Recombinant laminin 5

ABSTRACT

The present invention provides recombinant laminin 5, methods for making recombinant laminin 5, cells that express recombinant laminin 5, and methods for using the recombinant laminin 5 to accelerate wound healing, and to promote cell attachment and migration.

CROSS REFERENCE

[0001] This application claims priority to U.S. Provisional PatentApplication Serial No. 60/131,720 filed Apr. 30, 1999; No. 60/149,738filed Aug. 19, 1999; and No. 60/155,945 filed Sep. 24, 1999, all ofwhich are incorporated herein by reference in their entirety.

FIELD OF THE INVENTION

[0002] This application relates to recombinant laminin 5 and methods forits use.

BACKGROUND OF THE INVENTION

[0003] Basal laminae (basement membranes) are sheet-like,cell-associated extracellular matrices that play a central role in cellgrowth, tissue development, and tissue maintenance. They are present invirtually all tissues, and appear in the earliest stages of embryonicdevelopment.

[0004] Basal laminae are central to a variety of architectural andcell-interactive functions. (See for example, Malinda and Kleinman, Int.J. Biochem. Cell Biol. 28:957-959 (1996); Aumailley and Krieg, J.Invest. Dermatology 106:209-214 (1996)):

[0005] 1. They serve as architectural supports for tissues, providingadhesive substrates for cells.

[0006] 2. They create perm-selective barriers between tissuecompartments that impede the migration of cells and passively regulatethe exchange of macromolecules. These properties are illustrated by thekidney glomerular basement membrane, which functions as an importantfiltration structure, creating an effective blood-tissue barrier that isnot permeable to most proteins and cells.

[0007] 3. Basal laminae create highly interactive surfaces that canpromote cell migration and cell elongation during embryogenesis andwound repair. Following an injury, they provide a surface upon whichcells regenerate to restore normal tissue function.

[0008] 4. Basal laminae present information encoded in their structureto contacting cells that is important for differentiation and tissuemaintenance. This information is communicated to the cells throughvarious receptors that include the integrins, dystroglycan, and cellsurface proteoglycans. Signaling is dependent not only on the presenceof matrix ligands and corresponding receptors that interact withsufficient affinities, but also on such topographical factors as liganddensity in a three-dimensional matrix “landscape”, and on the ability ofbasal lamina components to cluster receptors. Because these matrixproteins can be long-lived, basal laminae create a “surface memory” inthe basal lamina for resident and transient cells.

[0009] The basal lamina is largely composed of laminin and type IVcollagen heterotrimers that in turn become organized into complexpolymeric structures. To date, six type IV collagen chains and at leasttwelve laminin chains (and twelve different heterotrimeric laminins)have been identified. These chains possess shared and unique functionsand are expressed with specific temporal (developmental) and spatial(tissue-site specific) patterns.

[0010] Laminins are a family of heterotrimeric glycoproteins that resideprimarily in the basal lamina. They function via binding interactionswith neighboring cell receptors, and are important signaling moleculesthat can strongly influence cellular function. Laminins are important inboth maintaining cell/tissue phenotype as well as promoting cell growthand differentiation in tissue repair and development.

[0011] Laminins are large, multi-domain proteins, with a commonstructural organization. The laminin molecule integrates various matrixand cell interactive functions into one molecule.

[0012] The laminin molecule is comprised of α-, β-, and γ-chains joinedtogether through a coiled-coil domain. Within this structure areidentifiable domains that possess binding activity towards other lamininand basal lamina molecules, and membrane-bound receptors. Domains VI,IVb, and IVa form globular structures, and domains V, IIIb, and IIIa(which contain cysteine-rich EGF-like elements) form rod-likestructures. (Kamiguchi et al., Ann. Rev. Neurosci. 21:97-125 (1998))Domains I and II of the three chains participate in the formation of atriple-stranded coiled-coil structure (the long arm).

[0013] Table 1 shows the individual chains that each laminin type iscomposed of: TABLE 1 Known laminin family members Protein ChainsLaminin-1 α1β1γ1 Laminin-2 α2β1γ1 Laminin 3 α1β2γ1 Laminin-4 α2β2γ1Laminin-5 α3β3γ2 Laminin-6 α3β1γ1 Laminin-7 α3β2γ1 Laminin-8 α4β1γ1Laminin-9 α4β2γ1 Laminin-10 α5β1γ1 Laminin-11 α5β2γ1 Laminin-12 α2β1γ3

[0014] Four structurally-defined family groups of laminins have beenidentified. The first group of five identified laminin molecules allshare the β1 and γ1 chains, and vary by their α-chain composition (α1 toα5 chain). The second group of five identified laminin molecules allshare the β2 and γ1 chain, and again vary by their α-chain composition.The third group of identified laminin molecules has one identifiedmember, laminin 5, with a chain composition of α3β3γ2. The fourth groupof identified laminin molecules has one identified member, laminin 12,with the newly identified γ3 chain (α2β1γ3)

[0015] Some progress has been made in elucidating the relationshipbetween domain structure and function. (See, for example, Wewer andEngvall, Neuromusc. Disord. 6:409-418 (1996).) The overall sequencesimilarity among the homologous domains in different chains varies, butit is highest in domain VI (thought to play a key role in lamininpolymerization), followed by domains V (possibly involved inprotein-protein-interactions) and III (entactin/nidogen binding;possible cell adhesion sites), and is lowest in domains I, II (boththought to be involved in intermolecular assembly, and containingpossible cell adhesion sites), and G. Not all domains are present in all3 types of chains. The globular G domain (thought to be involved in cellreceptor binding) is present only in the a chains. Other domains may notbe present in all chains within a certain chain type. For example,domain VI is absent from α3, α4, and γ2 chains. (Wewer and Engvall,1996)

[0016] As a result of their large size (>600 kD) and unique structure,the laminin molecules can be resolved in the electron microscope. (Wewerand Engvall, 1996) Typically, laminins appear as cross-shaped moleculesin an EM. The three short arms of the cross represent the amino terminalportions of each of the three separate laminin chains (one short arm perchain). The long arm of the cross is composed of the C-terminal parts ofthe three chains, which together form a coiled coil structure. (Wewerand Engvall, 1996) The long arm ends with the globular G domain.

[0017] The coiled-coil domain of the long arm is crucial for assembly ofthe three chains of laminin. (Yurchenco et al., Proc. Natl. Acad. Sci.94:10189-10194 (1997)). Disulfide bonds bridge and stabilize all threechains in the most proximal region of the long arm and join the β and γchains in the most distal region of the long arm.

[0018] A model of laminin receptor-facilitated self-assembly, based onstudies conducted with cultured skeletal myotubes and Schwann cells,predicts that laminins bind to their receptors, which freely diffuse ina fluidic membrane, when ligand-free. Receptor engagement forces thesereceptors into a high local two-dimensional concentration, facilitatingtheir mass-action driven assembly into ordered surface polymers. In thisprocess, the engaged receptors are also reorganized, accompanied bycytoskeletal rearrangements. (Colognato, J. Cell Biol. 145:619-631(1999)) This reorganization activates the receptors, causing signaltransduction with the alteration of cell expression, shape and/orbehavior.

[0019] One class of laminin receptors are the integrins, which are cellsurface receptors that mediate many cell-matrix and cell-cellinteractions. Integrins are heterodimers, consisting of an α and a βsubunit. 16 α- and 8 β-subunits are known, and at least 22 combinationsof a and β subunits have been identified to date. Some integrins haveonly one or a few known ligands, whereas others appear to be verypromiscuous. Binding to integrins is generally of low affinity, and isdependent on divalent cations. Integrins, activated through binding totheir ligands, transduce signals via kinase activation cascades, such asfocal adhesion and mitogen-activated kinases. Several differentintegrins bind different laminin isoforms more or less specifically.(Aumailley et al., In The Laminins, Timpl and Ekblom, eds., HarwoodAcademic Publishers, Amsterdam. pp. 127-158 (1996))

[0020] Laminin-5, also referred to as kalinin, nicein, and epiligrin,plays a key role in modulating the behavior and activity of cells andtissues of epithelial origin, and is expected to have broad uses inclinical settings where increased epithelial attachment andhemidesmosome assembly are required. (Takeda et al., J. Invest.Dermatol. 1999 113(1):38-42) Laminin-5 is a principal adhesive ligand inthe epidermal basal lamina, and has been shown to promote the attachmentof keratinocytes and epithelial cells to the basal lamina and underlyingdermis, and also promotes hemidesmosome formation. (Burgeson et al. U.S.Pat. No. 5,770,562; Quaranta and Hormia, U.S. Pat. No. 5,422,264; Jones,U.S. Pat. No. 5,541,106; Quaranta and Hormia, U.S. Pat. No. 5,658,789;Hormia et al., J. Invest. Dermatol. 1995 Oct. 105(4):557-561).

[0021] Laminin 5 is also thought to be necessary for the healing ofepithelial tissue wounds. (Goldfinger et al., J. Cell Sci. 1999; 112(Pt.16):2615-2629) Pretreatment of human keratinocyte sheets for graftingwith laminin 5 improves grafting efficiency. (Takeda et al., J. Invest.Dermatol. July 1999; 113(1):38-42). The addition of laminin-5accelerates the formation of a basement membrane in a skin equivalentmodel (Tsunenaga et al., Matrix Biol. 17(8-9):603-613, 1998). Laminin-5also promotes epithelial cell attachment to a wide variety ofbiomaterials, including polymers, hydroxyapatite, and metals. (Jones etal., U.S. Pat. No. 5,585,267; El Ghannam et al., J. Biomed. Mater. Res.July 1998; 41(1):30-40) Laminin 5 has further been demonstrated topromote the following:

[0022] 1. Epithelial cell adhesion to the internal basal lamina of teeth(Mullen et al., J. Periodontal. Res. January 1999 34(1):16-24; Hormia etal., J. Dent. Res. July 1998; 77(7):1479-1485) and anchorage ofameloblasts (ie: enamel-producing cells) to the enamel matrix. (Yoshibaet al., Cell Tissue Res. April 1998; 292(1):143-149)

[0023] 2. Corneal epithelial cell adhesion. (Qin and Kurpakus, Exp. EyeRes. May 1998 66(5):569-579)

[0024] 3. Intestinal epithelial restitution. (Lotz et al., Am. J.Pathol. February 1997;150(2):747-760)

[0025] 4. In vitro expansion of epithelial cells by providing anefficient adhesion substrate for primary cell cultures, thus providingthe basis for a wide range of new cell therapy applications. (Gonzaleset al., Mol. Biol. Cell. February 1999; 10(2):259-270; Baker et al.,Exp. Cell Res. Nov. 1, 1996; 228(2)262-270).

[0026] 5. Proliferation of pancreatic beta islet cells (Todorov et al.,Transplant. Proc. March 1998; 30(2): 455; Quaranta and Jones, U.S. Pat.No. 5,510,263; Halberstadt et al, U.S. Pat. No. 5,681,587; Halberstadtet al., U.S. Pat. No. 5,672,361), and T cells (Vivinus-Nebot et al., J.Cell Biol. Feb. 8, 1999; 144(3):563-574)

[0027] Thus, laminin 5 has broad uses in clinical settings whereincreased epithelial attachment and hemidesmosome assembly are required.Laminin 5 can be used to promote wound healing and tissue regeneration.The application of exogenous laminin 5 has broad application for theaccelerated healing of skin disorders, such as diabetic foot ulcers,venous ulcers, pressure sores, skin surgery, burns, and acute wounds.Exogenous laminin 5 may be used to directly treat a wound surface, ormay be applied to a variety of medical devices and dermal grafts forskin, corneal, gastrointestinal, and periodontal epithelial woundhealing. The use of laminin 5 provides enhanced biocompatibility of thedevice or graft, which leads to improved tissue integration andremodeling, reduced immune response, and reduced likelihood ofinfection. Laminin 5 is also useful for the ex vivo and in vitroproliferation of various cell types, including but not limited toepithelial cells, pancreatic beta islet cells, and T cells, and tissueequivalents. Thus, a source of laminin 5 for tissue culture media or amedia supplement, as well as cell-growth substrates coated with laminin5, would be particularly useful for the cultivation of these and othercell types.

[0028] A good source and purification procedure for laminin-5 is neededto provide material for the development of the therapeutic and researchapplications mentioned above. Some cell lines secrete laminin-5, andprocedures have been developed to purify laminin-5 from the processedcells and cell media. However, these methods are time consuming andcapable of producing only small amounts of laminin 5. (Rouselle et al.,J. Biol. Chem. 1995 270(23):13766-13770; Cheng et al., J. Biol. Chem.1997, 272(50):31525-31532)

[0029] A preferred method of production, however, is the use ofrecombinant DNA technology to engineer a cell line of choice to producerecombinant laminin-5. A recombinant-based method of laminin-5production has several advantages over purification from tissue orisolation from cell lines in culture:

[0030] 1. The recombinant produced protein is free of pathogens. Whilethis is also true for endogenous cell culture produced protein, proteinderived from human tissue carries a risk for contamination by HIV,hepatitis, and other infectious agents.

[0031] 2. Expression levels of the protein, and hence yields, can beimproved through the use of genetically engineered genes/vectors thatenhance the production of the encoded protein.

[0032] 3. It is possible to engineer additional peptide sequences to theprotein chain that provides a binding site for a commercially viableaffinity purification procedure.

[0033] 4. The method can provide for the modification of proteinstructure/function through the addition, substitution, elimination,and/or other modifications of protein domain structures. For example, itmay be desirable to introduce an integrin binding site (e.g. RGD),switch integrin recognition sites, or engineer in a stable binding siteto a synthetic substrate. Thus, the creation of expression vectors thatexpress laminin chains generates enormous flexibility for future usesand creates a basis for creating second generation “designer” laminins.

[0034] Previous studies have produced cells transfected with one or twoof the laminin 5 chain-encoding DNA sequences, but none have producedrecombinant heterotrimeric laminin 5, not have they produced cell linesthat secrete recombinant heterotrimeric laminin 5. (Gagnoux-Palacios etal., J. Biol. Chem. 271:18437-18444 (1996); Matsui et al., J. Biol.Chem. 270:23496-23503 (1995))

[0035] Thus, there exists a need in the art for recombinantheterotrimeric laminin 5 protein, methods for mailing recombinantlaminin 5, and methods of using recombinant laminin 5 for wound healingand tissue regeneration, for use on a variety of medical devices anddermal grafts for skin, corneal, gastrointestinal, and periodontalepithelial wound healing, for the ex vivo and in vitro proliferation ofvarious cell types, and for tissue culture media, media supplements, andas a component of cell growth substrates.

SUMMARY OF THE INVENTION

[0036] The present invention fulfills the need in the art forrecombinant laminin 5 protein, methods for making recombinant laminin 5,and methods of using recombinant laminin 5 for the treatment of burns,for use on a variety of medical devices and dermal grafts for skin,corneal, gastrointestinal, and periodontal epithelial wound healing, forthe ex vivo and in vitro proliferation of various cell types, and fortissue culture media, media supplements, and as a component of cellgrowth substrates.

[0037] In one aspect, the present invention provides cells that havebeen transfected with nucleic acid sequences encoding laminin α3, β3 andγ2 chains, wherein the cells express the individual chains, whichassemble into heterotrimeric recombinant laminin-5 (hereinafter referredto as “r-laminin 5”). r-laminin 5, or processed forms thereof, aresecreted by the cell.

[0038] In another aspect, the present invention provides r-laminin 5,and methods for producing substantially purified r-laminin 5, orprocessed forms thereof.

[0039] In a further aspect, the present invention providespharmaceutical compositions, comprising r-laminin 5, or processed formsthereof, together with a pharmaceutically acceptable carrier. Suchpharmaceutical compositions can optionally be provided with othercompounds with wound healing and tissue regeneration utility, such asother extracellular matrix components.

[0040] In further aspect, the present invention provides methods andkits for using r-laminin 5 to:

[0041] a. accelerate wound healing and tissue regeneration;

[0042] b. enhance the performance of skin grafts;

[0043] c. improve the attachment of gum tissue to the tooth surface;

[0044] d. improve the biocompatibility of medical devices; and

[0045] e. accelerate cell proliferation,

[0046] by providing an amount effective of r-laminin 5 for the variousmethods. The invention also provides methods and kits for using laminin5 to regulate angiogenesis. The kits comprise an amount of laminin 5 orr-laminin 5 effective for the desired effect, and instructions for theuse thereof.

[0047] In a further aspect, the present invention provides improvedmedical devices and grafts, wherein the improvement comprises coatingthe devices or grafts with an amount effective of r-laminin 5 or thepharmaceutical compositions of the invention for the desiredapplication.

[0048] In a further aspect, the invention provides improved cell culturedevices for the proliferation of cells in culture, by providing anamount effective of r-laminin 5 for the attachment of cells to a cellculture device for the attachment and subsequent proliferation,differentiation, or maintenance of the cells.

[0049] In another aspect, the invention provides a cell culture growthsupplement, comprising r-laminin 5. In another aspect, the inventionprovides an improved cell culture growth media, wherein the improvementcomprises the addition of r-laminin 5.

BRIEF DESCRIPTION OF THE FIGURES

[0050]FIG. 1 is a bar graph showing the results of an HFK cell adhesionassay for r-laminin 5 activity in culture media from various clones.

[0051]FIG. 2 is a bar graph showing a cell adhesion assay in whichr-laminin 5 was coated directly onto the plate. p1b5=anti-integrin α3β1antibody; sp2=control IgG, non-specific; C29: anti-laminin 5 antibody

[0052]FIG. 3 is a rotary shadow analysis of-r-laminin 5. Purifiedr-laminin 5 protein was diluted to 50 μg/ml and adjusted to 70%glycerol/30% 0.15M ammonium bicarbonate and rotary shadowed usingstandard techniques. An approximately 80,000× magnification field isshown of (A) r-laminin 5; (B) “native” laminin 5 (purified by BM165monoclonal antibody affinity chromatography from SCC-25 (squamous cellcarcinoma cell line) conditioned medium). The bar represents 50 nm.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0053] All references, patents and patent applications are herebyincorporated by reference in their entirety.

[0054] Within this application, unless otherwise stated, the techniquesutilized may be found in any of several well-known references such as:Molecular Cloning: A Laboratory Manual (Sambrook, et al., 1989, ColdSpring Harbor Laboratory Press), Gene Expression Technology (Methods inEnzymology, Vol. 185, edited by D. Goeddel, 1991. Academic Press, SanDiego, Calif.), “Guide to Protein Purification” in Methods in Enzymology(M. P. Deutshcer, ed., (1990) Academic Press, Inc.); PCR Protocols: AGuide to Methods and Applications (Innis, et al. 1990. Academic Press,San Diego, Calif.), Culture of Animal Cells: A Manual of BasicTechnique, 2^(nd) Ed. (R. I. Freshney. 1987. Liss, Inc. New York, N.Y.),Gene Transfer and Expression Protocols, pp. 109-128, ed. E. J. Murray,The Humana Press Inc., Clifton, N.J.), and the Ambion 1998 Catalog(Ambion, Austin, Tex.).

[0055] As used herein “laminin 5” encompasses both r-laminin 5 andheterotrimeric laminin 5 from naturally occurring sources.

[0056] The term “r-laminin 5” refers to include recombinantheterotrimeric laminin 5 expressed by a cell that has been exogenouslytransfected with expression vector(s) comprising polynucleotides thatencode α3, β3 and γ2 laminin polypeptide chains, or a portion of each ofthe chains which are capable of forming a heterotrimeric laminin 5, aswell as versions thereof resulting from cellular processing events. Suchr-laminin 5 can comprise α3, β3, and γ2 sequences from a singleorganism, or from different organisms. Laminin 5 chain DNA sequences andtheir encoded proteins from a variety of organisms are known in the art.(See, for example, Gerecke et al., J. Biol. Chem. 269:11073-11080(1994); Kallunki et al., J. Cell Biol. 119:679-693 (1992); Ryan et al.,J. Biol. Chem. 269:22779-22787 (1994); Iivananinen et al., J. Biol.Chem. 274:14107-14111 (1999); Galliano et al., J. Biol. Chem.270:21820-221826 (1995); Sugiyama et al., Eur. J. Biochem. 228:120-128(1995) all references incorporated by reference herein in theirentirety).

[0057] In the present invention, r-laminin 5 is a secreted protein,which is capable of being directed to the ER, secretory vesicles, andthe extracellular space as a result of a signal sequence, as well asthose proteins released into the extracellular space without necessarilycontaining a signal sequence. If the secreted protein is released intothe extracellular space, the secreted protein can undergo extracellularprocessing to produce a “mature” protein. Such processing event can bevariable, and thus may yield different versions of the final “matureprotein”. The substantially purified r-laminin 5 of the presentinvention includes heterotrimers comprising both the full length and anysuch processed laminin 5 chains.

[0058] As used herein, the term “substantially purified” means that therecombinant laminin 5 so designated has been separated from its in vivocellular environments.

[0059] As used herein, a laminin 5 polypeptide chain refers to apolypeptide chain according to one or more of the following:

[0060] (a) comprises a polypeptide structure selected from the groupconsisting of:

[0061] 1. R1-R2-R3

[0062] 2. R1-R2-R3(e)

[0063] 3. R3

[0064] 4. R3(e)

[0065] 5. R1-R3

[0066] 6. R1-R3(e)

[0067] 7. R2-R3

[0068] 8. R2-R3(e)

[0069] wherein R1 is a amino terminal methionine; R2 is a signalsequence that is capable of directing secretion of the polypeptide,wherein the signal sequence may be the natural signal sequence for theparticular laminin chain, that of another secreted protein, anartificial sequence; R3 is a secreted laminin chain selected from theα3, β3, and γ2 chains; and R3(e) is a secreted laminin chain selectedfrom the α3, β3, and γ2 chains that further comprises an epitope tag(such as those described below), which can be placed at any positionwithin the laminin chain amino acid sequence; and/or

[0070] (b) is encoded by a polynucleotide that is substantially similarto the disclosed laminin polynucleotide sequences or portions thereof(SEQ ID NOS.: 1, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27, 29, 31,33, 35); and/or

[0071] (c) is encoded by a polynucleotide that hybridizes under high orlow stringency conditions to coding regions, or portions thereof, of oneor more of the recombinant laminin 5 chain DNA sequences disclosedherein (SEQ ID NOS.: 1, 3, 5, 7, 9, 11, 13, 15, 17, 19, 21, 23, 25, 27,29, 31, 33, 35), or complementary sequences thereof; and/or

[0072] (d) has at least 70% identity to the disclosed lamininpolypeptide claim amino acid sequences (SEQ ID NOS.: 2, 4, 6, 8, 10, 12,14, 16, 18, 20, 22, 24, 26, 28, 30, 32, 34, 36), preferably at least 80%identity, and most preferably at least about 90% identity.

[0073] The phrase “substantially similar” is used herein in reference topolynucleotide or polypeptide sequences having one or more conservativevariations from the laminin 5 sequences disclosed herein, including butnot limited to deletions, insertions, inversions, repeats, andsubstitutions, wherein the resulting laminin chain is functionallyequivalent to those disclosed herein.

[0074] For example, conservative polynucleotide variants may containalterations in the coding regions, non-coding regions, or both.Especially preferred are polynucleotide variants containing alterationswhich produce silent substitutions, additions, or deletions, but do notalter the properties or activities of the encoded polypeptide.Nucleotide variants produced by silent substitutions due to thedegeneracy of the genetic code are preferred. Moreover, variants inwhich 5-10, 1-5, or 1-2 amino acids are substituted, deleted, or addedin any combination are also preferred. Polynucleotide variants can beproduced for a variety of reasons, including but not limited tooptimizing codon expression for a particular host (change codons in thehuman mRNA to those preferred by a bacterial host such as E. coli).

[0075] Naturally occurring conservative variants are called “allelicvariants,” and refer to one of several alternate forms of a geneoccupying a given locus on a chromosome of an organism. (Genes II,Lewin, B., ed., John Wiley & Sons, New York (1985).) These allelicvariants can vary at either the polynucleotide and/or polypeptide level.Alternatively, non-naturally occurring conservative variants may beproduced by mutagenesis techniques or by direct synthesis.

[0076] Using known methods of protein engineering and recombinant DNAtechnology, conservative polynucleotide variants may be generated toimprove or alter the characteristics of the expressed laminin chainpolypeptides. For instance, one or more amino acids can be deleted fromthe N-terminus or C-terminus of the secreted protein. (See, for example,Ron et al., J. Biol. Chem. 268: 2984-2988 (1993); Dobeli et al., J.Biotechnology 7:199-216 (1988)) Ample evidence demonstrates thatvariants often retain a biological activity similar to that of thenaturally occurring protein. (See, for example, Gayleet al., J. Biol.Chem 268:22105-22111 (1993)) Furthermore, even if deleting one or moreamino acids from the N-terminus or C-terminus of a polypeptide resultsin modification or loss of one or more biological functions, otherbiological activities may still be retained.

[0077] Guidance concerning how to make phenotypically silent amino acidsubstitutions is provided in Bowie, J. U. et al., Science 247:1306-1310(1990), wherein the authors indicate that there are two main strategiesfor studying the tolerance of an amino acid sequence to change.

[0078] The first strategy exploits the tolerance of amino acidsubstitutions by natural selection during the process of evolution. Bycomparing amino acid sequences in different species, conserved aminoacids can be identified. These conserved amino acids are likelyimportant for protein function. In contrast, the amino acid positionswhere substitutions have been tolerated by natural selection indicatesthat these positions are not critical for protein function. Thus,positions tolerating amino acid substitution could be modified whilestill maintaining biological activity of the protein.

[0079] The second strategy uses genetic engineering to introduce aminoacid changes at specific positions of a cloned gene to identify regionscritical for protein function. For example, site directed mutagenesis oralanine-scanning mutagenesis (introduction of single alanine mutationsat every residue in the molecule) can be used. (Cunningham and Wells,Science 244:1081-1085 (1989).) The resulting mutant molecules can thenbe tested for biological activity.

[0080] As the authors state, these two strategies have revealed thatproteins are surprisingly tolerant of amino acid substitutions. Theauthors further indicate which amino acid changes are likely to bepermissive at certain amino acid positions in the protein. For example,most buried (within the tertiary structure of the protein) amino acidresidues require nonpolar side chains, whereas few features of surfaceside chains are generally conserved. Moreover, tolerated conservativeamino acid substitutions involve replacement of the aliphatic orhydrophobic amino acids Ala, Val, Leu and Ile; replacement of thehydroxyl residues Ser and Thr; replacement of the acidic residues Aspand Glu; replacement of the amide residues Asn and Gln, replacement ofthe basic residues Lys, Arg, and His; replacement of the aromaticresidues Phe, Tyr, and Trp, and replacement of the small-sized aminoacids Ala, Ser, Thr, Met, and Gly.

[0081] The “substantially similar” polypeptides of the present inventionalso include (i) substitutions with one or more of the non-conservedamino acid residues, where the substituted amino acid residues may ormay not be one encoded by the genetic code, or (ii) substitution withone or more of amino acid residues having a substituent group; (iii)fusion of the mature polypeptide with another compound, such as acompound to increase the stability and/or solubility of the polypeptide(for example, polyethylene glycol); and/or (iv) fusion of thepolypeptide with additional amino acids, such as an IgG Fc fusion regionpeptide, or leader or secretory sequence, or a sequence facilitatingpurification. Such variant polypeptides are deemed to be within thescope of those skilled in the art from the teachings herein.

[0082] For example, polypeptide variants containing amino acidsubstitutions of charged amino acids with other charged or neutral aminoacids may produce proteins with improved characteristics, such as lessaggregation. Aggregation of pharmaceutical formulations both reducesactivity and increases clearance due to the aggregate's immunogenicactivity. (Pinckard et al., Clin. Exp. Immunol. 2:331-340 (1967);Robbins et al., Diabetes 36: 838-845 (1987); Cleland et al., Crit. Rev.Therapeutic Drug Carrier Systems 10:307-377 (1993).)

[0083] “Stringency of hybridization” is used herein to refer toconditions under which nucleic acid hybrids are stable. The inventionalso includes nucleic acids that hybridize under high stringencyconditions (as defined herein) to all or a portion of the codingsequences of the laminin chain polynucleotides disclosed herein, ortheir complements. The hybridizing portion of the hybridizing nucleicacids is typically at least 50 nucleotides in length. As known to thoseof skill in the art, the stability of hybrids is reflected in themelting temperature (T_(M)) of the hybrids. T_(M) decreasesapproximately 1-1.5° C. with every 1% decrease in sequence homology. Ingeneral, the stability of a hybrid is a function of sodium ionconcentration and temperature. Typically, the hybridization reaction isperformed under conditions of lower stringency, followed by washes ofvarying, but higher, stringency. Reference to hybridization stringencyrelates to such washing conditions. Thus, as used herein, highstringency refers to an overnight incubation at 42° C. in a solutioncomprising 50% formamide, 5×SSC (750 mM NaCl, 75 mM sodium citrate), 50mM sodium phosphate (pH 7.6), 5× Denhardt's solution, 10% dextransulfate, and 20 μg/ml denatured, sheared salmon sperm DNA, followed bywashing the filters in 0.1×SSC at about 65° C.

[0084] Also contemplated are laminin 5-encoding nucleic acid sequencesthat hybridize to the polynucleotides of the present invention at lowerstringency hybridization conditions. Changes in the stringency ofhybridization and signal detection are primarily accomplished throughthe manipulation of formamide concentration (lower percentages offormamide result in lowered stringency); salt conditions, ortemperature. For example, lower stringency conditions include anovernight incubation at 37° C. in a solution comprising 6×SSPE(20×SSPE=3M NaCl; 0.2M NaH₂PO₄; 0.02M EDTA, pH 7.4), 0.5% SDS, 30%formamide, 100 ug/ml salmon sperm blocking DNA; followed by washes at50° C. with 1×SSPE, 0.1% SDS. In addition, to achieve even lowerstringency, washes performed following stringent hybridization can bedone at higher salt concentrations (e.g. 5×SSC).

[0085] Note that variations in the above conditions may be accomplishedthrough the inclusion and/or substitution of alternate blocking reagentsused to suppress background in hybridization experiments. Typicalblocking reagents include Denhardt's reagent, BLOTTO, heparin, denaturedsalmon sperm DNA, and commercially available proprietary formulations.The inclusion of specific blocking reagents may require modification ofthe hybridization conditions described above, due to problems withcompatibility.

[0086] As used herein, “percent identity” of two amino acids or of twonucleic acids is determined using the algorithm of Karlin and Altschul(Proc. Natl. Acad. Sci. USA 87:2264-2268, 1990), modified as in Karlinand Altschul (Proc. Natl. Acad. Sci. USA 90:5873-5877, 1993). Such analgorithm is incorporated into the NBLAST and XBLAST programs ofAltschul et al. (J. Mol. Biol. 215:403-410, 1990). BLAST nucleotidesearches are performed with the NBLAST program, score=100,wordlength=12, to obtain nucleotide sequences homologous to the nucleicacid molecules of the invention. BLAST protein searches are performedwith the XBLAST program, score=50, wordlength=3, to obtain an amino acidsequence homologous to a polypeptide of the invention. To obtain gappedalignments for comparison purposes, Gapped BLAST is utilized asdescribed in Altschul et al. (Nucleic Acids. Res. 25:3389-3402, 1997).When utilizing BLAST and Gapped BLAST programs, the default parametersof the respective programs (e.g., XBLAST and NBLAST) are used. Seehttp://www.ncbi.nlm.nih.gov.

[0087] Further embodiments of the present invention includepolynucleotides encoding laminin chain polypeptides having at least 70%identity, preferably at least 80% identity, and most preferably at least90% identity to one or more polypeptide sequences, or fragments thereof,contained in SEQ ID NO:2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26,28, 30, 32, and 34.

[0088] As used herein, “α3 polynucleotide” refers to polynucleotidesencoding an α3 laminin chain of the same name. Such polynucleotides canbe characterized by one or more of the following: (a) the nucleotides ofsaid polynucleotide may encode an amino acid sequence substantiallysimilar to one or more of the sequences set forth in SEQ ID NO: 2, 4, 6,8, 10, 12 or fragments thereof, or fragments thereof; (b)polynucleotides that encode polypeptides which share at least 70%identity, preferably 80% identity, and most preferably at least 90%identity with one or more of the sequences set forth in SEQ ID NO: 2, 4,6, 8, 10, 12 or fragments thereof; (c) the α3 polynucleotides hybridizeunder low or high stringency conditions to the coding sequence set forthin one or more of SEQ ID NO: 1, 3, 5, 7, 9, 11, fragments thereof, orcomplementary sequences thereof; (d) the α3 polynucleotides may encode apolypeptide with a general structure selected from (1) R1-R2-R3; (2)R1-R2-R3(e); (3) R3; (4) R3(e); (5) R1-R3; (6) R1-R3(e); (7) R2-R3; and(8) R2-R3(e); wherein R1 and R2 are as described above, and R3 and R3(e)are as described above but comprise secreted α3 chain polypeptides.

[0089] As used herein, “β3 polynucleotide” refers to polynucleotidesencoding a β3 laminin chain of the same name. Such polynucleotides canbe characterized by one or more of the following: (a) the nucleotides ofsaid polynucleotide may encode an amino acid sequence substantiallysimilar to one ore more of the sequences set forth in SEQ ID NO: 14, 16,18, 20, 22, 24, or fragments thereof; (b) polynucleotides that encodepolypeptides which share at least 70% identity, preferably at least 80%,and most preferably at least 90% identity with one or more of thesequences set forth in SEQ ID NO: 14, 16, 18, 20, 22, 24, or fragmentsthereof; (c) the β3 polynucleotides hybridize under low or highstringency conditions to the coding sequence of one or more of thesequences set forth SEQ ID NO: 13, 15, 17, 19, 21, 23, fragments thereofor complementary sequences thereof; (d) the β3 polynucleotides mayencode a polypeptide with a general structure selected from (1)R1-R2-R3; (2) R1-R2-R3(e); (3) R3; (4) R3(e); (5) R1-R3; (6) R1-R3(e);(7) R2-R3; and (8) R2-R3(e); wherein R1 and R2 are as described above,and R3 and R3(e) are as described above but comprise secreted β3 chainpolypeptides.

[0090] As used herein, “γ2 polynucleotide” refers to polynucleotidesencoding a γ2 laminin chain of the same name. Such polynucleotides canbe characterized by one or more of the following: (a) the nucleotides ofsaid polynucleotide may encode an amino acid that is substantiallysimilar to one or more of the sequences set forth in SEQ ID NO: 26, 28,30, 32, 34, 36 or fragments thereof; (b) polynucleotides that encodepolypeptides which share at least 70% identity, preferably at least 80%,and most preferably at least 90% identity with one or more of thesequences set forth in SEQ ID NO: 26, 28, 30, 32, 34, 36 or fragmentsthereof; (c) the γ2 polynucleotides hybridize under low or highstringency conditions to the coding sequence set forth in one or more ofSEQ ID NO: 25, 27, 29, 31, 33, 35, fragments thereof, or complementarysequences thereof; (d) the γ2 polynucleotides may encode a polypeptidewith a general structure selected from (1) R1-R2-R3; (2) R1-R2-R3(e);(3) R3; (4) R3(e); (5) R1-R3; (6) R1-R3(e); (7) R2-R3; and (8) R2-R3(e);wherein R1 and R2 are as described above, and R3 and R3(e) are asdescribed above but comprise secreted γ2 chain polypeptides.

[0091] As used herein, the term “epitope tag” refers to a polypeptidesequence that is expressed as part of a chimeric protein, where theepitope tag serves as a recognition site for binding of antibodiesgenerated against the epitope tag, or for binding of other moleculesthat can be used for affinity purification of sequences containing thetag.

[0092] As used herein, the term “increased biocompatibility” refers toreduced induction of acute or chronic inflammatory response, and reduceddisruption of the proper differentiation of implant-surrounding tissuesfor laminin 5-coated biomaterials relative to an analogous, non-coatedbiomaterial.

[0093] As used herein the term “graft” refers to both natural andprosthetic grafts and implants.

[0094] In one aspect, the present invention provides cells that havebeen systematically transfected with recombinant expression vectorscomprising promoter sequences that are operatively linked topolynucleotide sequences encoding polypeptide sequences comprising α3,β3, and γ2 laminin 5 chains. After the multiple transfections, the cellsexpress each of the recombinant laminin 5 chains, which assemble into aheterotrimer and can be purified from the cell culture medium.

[0095] In a preferred embodiment, cDNAs encoding proteins comprising theα3, β3, and γ2 laminin polypeptide chains, or fragments thereof, aresubcloned into an expression vector. Alternatively, laminin 5 α3, β3,and/or γ2 gene sequences, including one or more introns, and includingvarious 5′ and 3′ non-coding regions, can be used.

[0096] Any cell capable of expressing and secreting the r-laminin 5 canbe used. Preferably, eukaryotic cells are used, and most preferablymammalian cells are used, including but not limited to kidney andepithelial cell lines. Especially preferred are those mammalian cellsthat do not endogenously express laminin 5. Carbohydrate and disulfidepost-translational modifications are believed to be required for laminin5 protein folding and function. This makes the use of eukaryotic cellspreferable for producing functional r-laminin 5, although other systemsare useful for obtaining, for example, antigens for antibody production.

[0097] “Recombinant expression vector” includes vectors that operativelylink a nucleic acid coding region or gene to any promoter capable ofeffecting expression of the gene product. The promoter sequence used todrive expression of the laminin 5 individual chains may be constitutive(driven by any of a variety of promoters, including but not limited to,CMV, SV40, RSV, actin, EF) or inducible (driven by any of a number ofinducible promoters including, but not limited to, tetracycline,ecdysone, steroid-responsive). The expression vector must be replicablein the host organisms either as an episome or by integration into hostchromosomal DNA. In a preferred embodiment, the expression vectorcomprises a plasmid. However, the invention is intended to include otherexpression vectors that serve equivalent functions, such as viralvectors.

[0098] In one embodiment, at least one of the laminin chain polypeptidesequences, or fragments thereof, is operatively linked to a nucleic acidsequence encoding an “epitope tag”, so that at least one of the chainsis expressed as a fusion protein with an expressed epitope tag. Theepitope tag may be expressed as the amino terminus, the carboxyterminus, or internal to the end of a r-laminin 5 chain, so long as theresulting heterotrimeric r-laminin 5 remains functional. Any epitope tagmay be utilized, so long as it can be used as the basis for affinitypurification of the resulting r-laminin 5 heterotrimer. Examples of suchepitope tags include, but are not limited to FLAG (Sigma Chemical, St.Louis, Mo.), myc (9E10) (Invitrogen, Carlsbad, Calif.), 6-His(Invitrogen; Novagen, Madison, Wis.), and HA (Boehringer ManheimBiochemicals).

[0099] In another embodiment, one of the r-laminin 5 chains is expressedas a fusion protein with a first epitope tag, and at least one otherr-laminin chain is expressed as a fusion protein with a second epitopetag. This permits multiple rounds of purification to be carried out.Alternatively, the same epitope tag can be used to create fusionproteins with more than one of the r-laminin chains.

[0100] In a further embodiment, the epitope tag can be engineered to becleavable from the r-laminin 5 chain(s). Alternatively, no epitope tagis fused to any of the r-laminin 5 chains, and the r-laminin 5 ispurified by standard chromatography techniques, including but notlimited to affinity chromatography using laminin 5 specific antibodiesor other laminin 5 binding molecules, ionic exchange, hydrophobicexchange, etc.

[0101] Transfection of expression vectors into the host cells can beaccomplished via any technique known in the art, including but notlimited to standard bacterial transformation, calcium phosphateco-precipitation, electroporation, or liposome mediated-, DEAE dextranmediated-, polycationic mediated-, or viral mediated transfection.

[0102] In a preferred embodiment, the cells are stably transfected. Anymethods for stable transfection and selection of appropriate transfectedcells are known in the art. In a most preferred embodiment, a CMVpromoter driven expression vector is used in a human kidney embryonic293 cell line.

[0103] Media from cells transfected with a single laminin chain areinitially analyzed on Western blots using chain-specific anti-laminin-5antibodies. The expression of single laminin chains followingtransfection is generally intracellular. Clones showing reactivityagainst individual transfected chain(s) are verified by any appropriatemethod, such as PCR, reverse transcription-PCR, or nucleic acidhybridization, to confirm incorporation of the transfected gene.Preferably, analysis of genomic DNA preparations from such clones isdone by PCR using laminin chain-specific primer pairs. Media fromtransfected clones producing all three chains are further analyzed forheterotrimeric laminin 5 secretion and/or activity, by any appropriatemethod, including Western blot analysis and cell binding assays, such asa keratinocyte cell adhesion assay.

[0104] In another aspect, the present invention provides substantiallypurified r-laminin 5, comprising an α3 chain, a β3 chain, and a γ2chain, and methods for producing substantially purified r-laminin 5. Inone embodiment, the r-laminin 5 comprises a first chain comprising apolypeptide that is substantially similar to at least one of thesequences shown in SEQ ID NO:2, 4, 6, 8, 10, 12 or fragments thereof; asecond chain comprising a polypeptide that is substantially similar toat least one of the sequences shown in SEQ ID NO:14, 16, 18, 20, 22, 24,or fragments thereof; and a third chain comprising a polypeptide that issubstantially similar to at least one of the sequences shown in SEQ IDNO:26, 28, 30, 32, 34, 36, or fragments thereof, wherein the first,second, and third polypeptides are produced recombinantly, and whereinthe first, second, and third chains assemble into a recombinantheterotrimeric laminin 5.

[0105] In another embodiment, the substantially purified r-laminin 5comprises a first chain comprising a polypeptide that is at least about70% identical to at least one of the sequences shown in SEQ ID NO:2, 4,6, 8, 10, 12, or fragments thereof; a second chain comprising apolypeptide that is at least 70% identical to at least one of thesequences shown in SEQ ID NO:14, 16, 18, 20, 22, 24, or fragmentsthereof; and a third chain comprising a polypeptide that is at least 70%identical to at least one of the sequences shown in SEQ ID NO:26, 28,30, 32, 34, 36, or fragments thereof, wherein the first, second, andthird polypeptides assemble into a recombinant heterotrimeric laminin 5.

[0106] In a preferred embodiment, at least one of the first, second, orthird chains of the substantially purified human r-laminin 5 isexpressed as a fusion protein with an epitope tag.

[0107] Alternatively, the r-laminin 5 comprises a heterotrimericpolypeptide structure, wherein each individual chain comprises a generalstructure selected from the group consisting of: (1) R1-R2-R3; (2)R1-R2-R3(e); (3) R3; (4) R3(e); (5) R1-R3; (6) R1-R3(e); (7) R2-R3; and(8) R2-R3(e)

[0108] wherein R1 is a amino terminal methionine; R2 is a signalsequence that is capable of directing secretion of the polypeptide,wherein the signal sequence may be the natural signal sequence for theparticular laminin chain, that of another secreted protein, or anartificial sequence; R3 is a secreted α3, β3, or γ2 laminin chain; andR3(e) is a secreted laminin α3, β3, and γ2 chain that further comprisesan epitope tag (such as those described above), which can be placed atany position within the laminin chain amino acid sequence.

[0109] In a preferred embodiment, purification of the r-laminin 5 isaccomplished by passing media from the transfected cells through anaffinity column. For example, antibodies or other binding molecules thatbind to a peptide epitope expressed on at least one of the recombinantchains are attached to an affinity column, and bind r-laminin 5 that hasbeen secreted into the media. The r-laminin 5 is removed from the columnby passing excess peptide through the column. The eluted protein cansubsequently be further purified, if desired.

[0110] Eluted fractions are analyzed by any appropriate method,including gel electrophoresis and Western blot analysis. In a furtherembodiment, the peptide epitope can be cleaved after purification. Inother embodiments, two or three separate r-laminin chains are expressedas fusion proteins, each with a different epitope tag, permitting two orthree rounds of purification and a doubly or triply purified r-laminin5. The epitope tag can be engineered so as to be cleavable from ther-laminin 5 chain(s) after purification. Alternatively, no epitope tagis fused to any of the r-laminin 5 chains, and the r-laminin 5 ispurified by standard techniques, including but not limited to affinitychromatography using laminin 5 specific antibodies or other laminin 5binding molecules.

[0111] In another aspect, the present invention provides novel lamininβ3 and γ2 chain nucleic acids and proteins, consisting of the nucleicacid sequences and proteins disclosed as SEQ ID NO:21-22, 23-24, 29-30,and 31-32.

[0112] The present invention further provides pharmaceuticalcompositions comprising r-laminin 5, as disclosed above, and apharmaceutically acceptable carrier. According to this aspect of theinvention, other agents can be included in the pharmaceuticalcompositions, depending on the condition being treated, including butnot limited to any of the collagens, other laminin types, fibronectin,integrins, glycoproteins, proteoglycans, heparan and heparan sulfateproteoglycans, growth factors such as vascular endothelial growth factor(VEGF), platelet derived growth factor (PDGF), and keratinocyte growthfactor (KGF); glycosaninoglycans, entactin, nidogen, and peptidefragments thereof.

[0113] Pharmaceutical preparations comprising r-laminin 5 can beprepared in any suitable form, and generally comprise the r-laminin 5 incombination with any of the well known pharmaceutically acceptablecarriers. The carriers can be injectable carriers, topical carriers,transdermal carriers, and the like. The preparation may advantageouslybe in a form for topical administration, such as an ointment, gel,cream, spray, dispersion, suspension or paste. The preparations mayfurther advantageously include preservatives, antibacterials,antifungals, antioxidants, osmotic agents, and similar materials incomposition and quantity as is conventional. Suitable solutions for usein accordance with the invention are sterile, are not harmful for theproposed application, and may be subjected to conventionalpharmaceutical operations such as sterilization and/or may containconventional adjuvants, such as preservatives, stabilizers, wettingagents, emulsifiers, buffers etc. For assistance in formulating thecompositions of the present invention, one may refer to Remington'sPharmaceutical Sciences, 15th Ed., Mack Publishing Co., Easton, Pa.(1975).

[0114] The dosage regimen for various treatments using the r-laminin 5of the present invention is based on a variety of factors, including thetype of injury or condition, the age, weight, sex, medical condition ofthe individual, the severity of the condition, and the route ofadministration. Thus, the dosage regimen may vary widely, but can bedetermined routinely by a physician using standard methods. Laminins areextremely potent molecules, and one or a few molecules per cell couldproduce an effect. Thus, effective doses in the pico-gram per milliliterrange are possible if the delivery is optimized. Laminins are sometimespresent in an insoluble form in the basement membrane and have thecapability of polymerizing at concentrations ranging as low as about 50μg/ml, depending on the laminin isoform and the conditions. Laminins canalso polymerize into a gel at a concentration of 2-3 mg/ml. Dosagelevels of the order of between 1 ng/ml and 10 mg/ml are thus useful forall methods disclosed herein, preferably between about 1 μg/ml and about3 mg/ml.

[0115] The treatment regime will also vary depending on the condition ofthe subject, based on a variety of factors, including the type ofinjury, the age, weight, sex, medical condition of the individual, theseverity of the condition, and the route of administration. For example,r-laminin 5 can be used to coat a wound dressing, which is placed incontact with a patient's wound as frequently as the dressing needs to bechanged, and for as long as the dressing is applied to the woundsurface.

[0116] Similarly, the route of administration will vary depending on thecondition of the subject, based on a variety of factors, including thetype of injury, the age, weight, sex, medical condition of theindividual, and the severity of the condition.

[0117] In further aspect, the present invention provides methods forusing r-laminin 5, or the pharmaceutical compositions of the invention,to accelerate wound healing and tissue regeneration. In preferredembodiments, r-laminin 5 is used to accelerate the healing of skin indiabetic foot ulcers, venous ulcers, pressure sores, skin surgery,severe burns, and acute wounds, and enhanced performance of skin grafts(both autologous and artificial). In another aspect, the presentinvention provides kits for carrying out these methods, comprising anamount effective of laminin 5 or r-laminin 5 and instructions for usingthe laminin 5 to carry out the methods.

[0118] In one embodiment, r-laminin 5, or a pharmaceutical compositioncomprising r-laminin 5, is used to enhance wound healing by promotingthe adhesion of transplanted cultured keratinocytes or other epithelialcells to an underlying substrate, such as a mammalian or human dermis.The substrate may comprise a wound surface, the basal surface of aconfluent layer of cultured epithelial cells to be transplanted, or asubstrate to be applied to the wound surface, such as a wound dressing,prior to placing the layer on a graft site. The r-laminin 5 may besupplied in a pharmaceutically acceptable carrier, preferably in amountsof between about 1 ng/ml and about 10 mg/ml.

[0119] The use of kalinin-containing (ie: laminin 5-containing) isolatedcell matrices has previously been shown to enhance the adhesion oftransplanted cultured keratinocytes to an underlying substrate (Burgesonet al., U.S. Pat. No. 5,770,562). This and other studies have thusdemonstrated that laminin 5 stimulates epithelial cell attachment andspreading, and thus provides an appropriate surface facilitating thehealing of skin and the use of skin grafts. (Quaranta and Hormia, U.S.Pat. No. 5,422,264; Jones, U.S. Pat. No. 5,541,106; Quaranta and Hormia,U.S. Pat. No. 5,658,789; Hormia et al., J. Invest. Dermatol. 1995 Oct.105(4):557-561; Takeda et al., J. Invest. Dermatol. 1999 July;113(1):38-42; Goldfinger et al., J. Cell Sci. 1999; 112(Pt.16):2615-2629).

[0120] Thus, the addition of r-laminin 5 to the appropriate injuredtissue can promote cell growth, cell migration, and accelerate tissueregeneration. Accelerated healing has the added benefit of reducinginflammatory responses and scarring. This can be accomplished in somecases by simply coating the r-laminin 5 or the pharmaceuticalcompositions of the invention into a wound area (such as skin,periodontal epithelial cells), or in other cases, by providing asuitable substrate to which r-laminin 5 has been anchored, including butnot limited to wound dressing and matrices, graft substrates, and dentalabutments.

[0121] The incorporation of recombinant r-laminin 5 into wound repairdressings and matrices as well as tissue grafts will provide a naturalligand interactive surface to promote normal cell adherence, cell growthand tissue development. Many grafts are used to replace tissue that hasan epithelial cell layer adherent to a basal lamina. When aninappropriate surface is provided to these cells following grafting, thegraft is at risk for failure of restoration of the normal cell layer.The advantage of coating these grafts with r-laminin 5 is to create asurface that sufficiently recapitulates a normal basal lamina surface topromote cell re-population.

[0122] Skin grafts are used in cases were large surface areas of skinhave been burned or injured. The application of r-laminin 5 and/or thepharmaceutical compositions of the invention will significantly promotethe attachment and ‘take’ of skin grafts to the injured tissue, as wellas promote normal skin healing processes while minimizing scar tissueformation.

[0123] Collagen-based matrices are also applied to serious skin injuriesto promote the growth of the underlying dermis and improve the take of askin graft. Coating the collagen matrices with r-laminin-5 will create amore natural ligand interactive surface to promote cell migration, cellproliferation and the regeneration of the dermis. An acceleration of theregeneration of the dermis, and take of the skin graft, will minimizescar tissue formation.

[0124] Purified laminin 5 has been demonstrated to support epithelialcell adhesion to the internal basal lamina of teeth (Mullen et al., J.Periodontal. Res. January 1999 34(1):16-24; Hormia et al., J. Dent. Res.July 1998; 77(7):1479-1485) and is believed to strengthen the anchorageof ameloblasts (ie: enamel-producing cells) to the enamel matrix.(Yoshiba et al., Cell Tissue Res. April 1998; 292(1):143-149). Thus, inanother embodiment, the r-laminin 5 or the pharmaceutical compositionsof the invention are used to stimulate epithelium cell adhesion to theinternal basal lamina of teeth and of ameloblasts to the enamel matrixof teeth. Such treatments are useful for the treatment of periodontaldiseases, including but not limited to oral ulcerations, gingivitis andperiodontitis. For example, existing teeth may be coated with ther-laminin 5 or the pharmaceutical compositions of the present inventionas a treatment for gum (junctional epithelium) diseases, including butnot limited to gingivitis and periodontitis, which promote thedetachment of the gum from the tooth. These disease conditions allow theaccumulation of food and other foreign matter in the space between thegum and the tooth, resulting in infection. The r-laminin 5 will promotereattachment of the gum to the tooth, thus preventing entry of foreignmatter and subsequent infection.

[0125] For use in treating gingivitis and other periodontal diseases anddisorders, the pharmaceutical compositions of the present invention maybe in the form of toothcreams, toothpastes, liquid dentifrices,tooth-powders chewing-gum, tablets and the like. The pharmaceuticalcompositions of the invention can also contain flavoring, coloringagents, sweeteners, preservatives, surface active agents, and the like.

[0126] Purified laminin-5 has been shown to promote the in vitroexpansion of epithelial cells (Gonzales et al., Mol. Biol. Cell.February 1999; 10(2):259-270; Baker et al., Exp. Cell Res. Nov. 1, 1996;228(2)262-270), pancreatic beta islet cells (Todorov et al., Transplant.Proc. March 1998; 30(2): 455; Quaranta and Jones, U.S. Pat. No.5,510,263; Halberstadt et al, U.S. Pat. No. 5,681,587; Halberstadt etal., U.S. Pat. No. 5,672,361), and T cells (Vivinus-Nebot et al., J.Cell Biol. Feb. 8, 1999; 144(3):563-574), by providing an efficientadhesion substrate for primary cell cultures. Thus, in another aspect ofthe present invention, r-laminin 5 is used to enhance the adhesion ofcells for proliferation, differentiation, or maintenance of cellsincluding, but not limited to pancreatic beta islet cells, epithelialcells, or T cells, by contacting the cells with an amount effective ofr-laminin 5 to provide an efficient adhesion substrate for attachmentand subsequent proliferation, differentiation, or maintenance of thecells. The r-laminin 5 can be provided in the cell culture medium, as acell culture medium supplement, or may be coated on the surface of acell growth substrate. In each case, r-laminin 5 is preferably used at aconcentration of between about 1 ng/ml and about 10 mg/ml. The cells canoptionally be contacted with other compounds that promote cell adhesion,proliferation, differentiation, and/or maintenance, including but notlimited to any of the collagens, other laminin types, fibronectin,integrins, glycoproteins, proteoglycans, heparan sulfate proteoglycan,glycosaminoglycans, entactin, nidogen, and peptide fragments thereof.

[0127] The cells may be primary cells or cell lines. The methods of thisaspect of the invention can be used in vivo, ex vivo, or in vitro.

[0128] In a preferred embodiment, r-laminin 5 is used to coat thesurface of a substrate to promote cell adhesion to the substrate, and tostimulate cell proliferation, differentiation, and/or maintenance. Thesubstrate used herein may be any desired substrate. For laboratory use,the substrate may be as simple as glass or plastic. For use in vivo, thesubstrate may be any biologically compatible material capable ofsupporting cell growth. Suitable substrate materials include shapedarticles made of or coated with such materials as collagen, regeneratedcollagen, polyglycolic acid, polygalactose, polylactic acid orderivatives thereof; biocompatible metals such as titanium and stainlesssteel; ceramic materials including prosthetic material such ashydroxylapatite; synthetic polymers including polyesters and nylons;polystyrene; polyacrylates; polytetrafluoroethylene, and virtually anyother material to which biological molecules can. readily adhere. Thedetermination of the ability of a particular material to supportadhesion of r-laminin 5 of the invention requires only routineexperimentation by the skilled artisan.

[0129] In a further aspect, the present invention provides a method oftreating Type I diabetes in a patient in need thereof comprisingcontacting pancreatic beta islet cells with an amount effective ofr-laminin 5 to provide an efficient adhesion substrate for the cells,leading to increased proliferation of insulin-producing pancreatic betaislet cells, and administering the cells to a patient in need thereof.

[0130] Nearly two million Americans are afflicted with Type I(insulin-dependent) diabetes, in which the pancreas has lost its abilityto secrete insulin due to an autoimmune disorder in which theinsulin-secreting beta cells, found within the islet cells of thepancreas, are destroyed. Although insulin injections can compensate forbeta cell destruction, blood sugar levels can still fluctuatedramatically. The impaired ability to take up glucose from the bloodresults in side reactions in which toxic products accumulate, leading tocomplications including blindness, kidney disease, nerve damage, and,ultimately, coma and death. (U.S. Pat. No. 5,672,361)

[0131] The pancreatic beta islet cells to be grown are plated on orapplied to the matrix-coated substrate using standard tissue culturetechniques, followed by expansion in standard cell growth medium (asdisclosed in U.S. Pat. No. 5,672,361) in the presence of r-laminin 5.Any medium capable of supporting the enhanced growth of adult isletcells on the matrix-coated substrate is within the scope of theinvention, as discussed above.

[0132] Fetal pancreatic islet cells may be grown in vitro in thepresence of r-laminin 5 for transplantation into diabetic patients.Growth of fetal pancreatic islet cells in the presence of r-laminin 5increases the yield of islet cells for transplantation and thus solvesthe need to produce larger amounts of these cells. In addition, it iscontemplated that the inclusion of other growth factors in the adultislet cell culture medium will further increase the yield of isletcells.

[0133] Laminins, or cell extracts containing laminins have been shown toregulate angiogenesis in a biphasic manner. (See, for example, Nicosiaet al., Dev. Biol. 164:197-206 (1994); Bonfil et al., Int. J. Cancer58:233-239 (1994)). At lower concentrations (30-300 μg/ml), alaminin-entactin complex stimulated angiogenesis in a three-dimensionalculture, while at 3000 μg/ml the same complex was inhibitory toangiogenesis. Thus, in another aspect, the present invention providesmethods for regulating angiogenesis, comprising contacting a tissue orculture substrate with an amount effective of laminin 5 orpharmaceutical compositions thereof to regulate angiogenesis. In oneembodiments, the laminin 5 is used to promote angiogenesis by contactinga tissue or culture substrate with an amount effective of laminin 5 topromote angiogenesis. In another embodiment, the laminin 5 is used toinhibit angiogenesis, by contacting the tissue or culture substrate withan amount effective of laminin 5 to inhibit angiogenesis. An example ofculture substrates to be contacted with laminin 5 to regulateangiogenesis are those used for tissue engineering purposes.

[0134] As used herein, the term “angiogenesis” refers to the formationof blood vessels. Specifically, angiogenesis is a multistep process inwhich endothelial cells focally degrade and invade through their ownbasement membrane, migrate through interstitial stroma toward anangiogenic stimulus, proliferate proximal to the migrating tip, organizeinto blood vessels, and reattach to newly synthesized basement membrane(see Folkman et al., Adv. Cancer Res., Vol. 43, pp. 175-203 (1985)).Compounds that promote angiogenesis can be used to promote wound healingand skin grafting, organ transplantation, (including artificial organs),acceleration of endothelial cell coverage of vascular grafts to preventgraft failure due to re-occlusion, to treat ischemic conditions, and totreat inflammatory diseases.

[0135] In a further aspect, the present invention provides cellsubstrates comprising an amount effective of r-laminin 5 for theadhesion, growth, or maintenance of cells in culture. The substrates maycomprise any of the substrates discussed above. Preferably, ther-laminin 5 is coated on the surface of the substrate using solution ata concentration of between about 1 ng/ml and about 10 mg/ml.

[0136] In another aspect of the present invention, an improved cellculture medium is provided, wherein the improvement comprises additionto the cell culture medium of an effective amount of r-laminin 5 to thecell culture medium to promote the adherence, proliferation, and/ormaintenance of cells. Any cell culture media that can support the growthof cells can be used with the present invention. Such cell culture-mediainclude, but are not limited to Basal Media Eagle, Dulbecco's ModifiedEagle Medium, Iscove's Modified Dulbecco's Medium, McCoy's Medium,Minimum Essential Medium, F-10 Nutrient Mixtures, Opti-MEM®Reduced-Serum Medium, RPMI Medium, and Macrophage-SFM Medium orcombinations thereof.

[0137] The improved cell culture medium can be supplied in either aconcentrated (ie: 10×) or non-concentrated form, and may be supplied aseither a liquid, a powder, or a lyophilizate. The cell culture may beeither chemically defined, or may contain a serum supplement. Culturemedia is commercially available from many sources, such as GIBCO BRL(Gaithersburg, Md.) and Sigma (St. Louis, Mo.). Alternatively, ther-laminin 5 is used as a cell culture supplement, and can be separatelyadded to the cell culture medium.

[0138] Purified laminin-5 has also been shown to promote epithelial cellattachment to a wide variety of biomaterials, including polymers,hydroxyapatite, and metals, thus improving the biocompatibility of thebiomaterials. (Jones et al., U.S. Pat. No. 5,585,267; El Ghannam et al.,J. Biomed. Mater. Res. July 1998; 41(1):30-40)

[0139] Thus, in a further aspect, the present invention comprisesmedical devices with improved biocompatibility, wherein the devices arecoated with the r-laminin 5 of the invention, alone or in combinationwith other proteins or agents that serve to increase thebiocompatibility of the device surface. The coated device stimulatescell attachment and provides for diminished inflammation and/orinfection at the site of entry of the appliance. The device may also beused to stimulate gum junctional epithelium adhesion in the treatment ofgingivitis and periodontitis.

[0140] Preferably, the device is a shaped article that is either anindwelling or transcutaneous catheter, polytetrafluoroethylene (PTFE),expanded PTFE (EPTFE), needle, metal pin, metal rod, colostomy tube,transcutaneous catheter, dental abutment piece or surgical mesh. Inanother aspect of this preferred embodiment, the device is used in vivo.Preferably, the appliance is made of or coated with a biocompatiblemetal that may be either stainless steel or titanium. Alternatively, thedevice is made of or coated with a ceramic material, or a polymerincluding but not limited to polyester, polyglycolic acid or apolygalactose-polyglycolic acid copolymer.

[0141] One particular use of the present invention is to increaseepithelial cell adhesion to target surfaces. For example, prostheses fordental implantation may be coated with the r-laminin 5 of the inventionto stimulate periodontal cell attachment. These prostheses typicallycomprise two separate pieces, an implant which is inserted into the boneand an abutment piece which actually contacts the junctional epithelium.Alternatively, the implant and abutment piece may be obtained as asingle unit.

[0142] If the device is made of a natural or synthetic biodegradablematerial in the form of a mesh, sheet or fabric, the r-laminin 5 may beapplied directly to the surface thereof. Epithelial cells may then becultured on the matrix to form transplantable or implantable devices,including dental abutment pieces, needles, metal pins or rods,indwelling catheters, colostomy tubes, surgical meshes and any otherappliance for which coating with the r-laminin is desirable.Alternatively, the devices may be implanted and cells may be permittedto attach in vivo. The epithelial cell-coated surgical meshes will beuseful for skin allografts necessitated by compromised skin integrity.

[0143] Coupling of the r-laminin 5 may be non-covalent (such as byadsorption), or by covalent means. The device may be immersed in,incubated in, or sprayed with the r-laminin 5 of the invention. In apreferred embodiment, the concentration of r-laminin 5 for coating thedevice is between about 1 ng/ml and about 10 mg/ml.

[0144] The present invention also provides a method for inducingepithelial cell attachment to the device (as disclosed above),comprising coating the appliance with r-laminin 5 prior to incubationwith epithelial cells.

[0145] The therapeutic application of r-laminin 5 produced in accordancewith the present invention can be used for the treatment of a variety ofconditions and diseases, including but not limited to Type I diabetes;skin conditions including but not limited to diabetic foot ulcers,venous ulcers, pressure sores, skin surgery, burns, acute wounds, andskin grafts; corneal ulcerations; gastro-intestinal ulcers;periodontitis; and gingivitis. The therapeutically effective amount ofr-laminin 5 for use in these conditions and diseases can be readilyascertained by one of ordinary skill in the art.

[0146] The present invention may be better understood with reference tothe accompanying examples that are intended for purposes of illustrationonly and should not be construed to limit the scope of the invention, asdefined by the claims appended hereto.

EXAMPLES

[0147] Production of r-laminin-5 involved sequential transfections of amammalian cell line with vectors containing cDNAs that encode for thechains of the laminin-5 molecule, namely α3, β3 and γ2. An additionalpolynucleotide sequence that encodes the ‘flag’ peptide (DYKDDDDK), wasadded to the amino terminus end of the β3 gene to facilitate affinitypurification of the expressed heterotrimeric recombinant laminin-5molecule.

[0148] IV. Materials and Methods

[0149] Expression Vector Constructs for α3

[0150] The entire coding sequence of the α3 cDNA [SEQ ID NO:1] wascloned via standard techniques into the expression vector pcDNA3.1/Zeo(Invitrogen), which contains the Zeocin resistant gene for selection.The expression vectors were used to produce stable cell lines accordingto the manufacturer's instructions.

[0151] In order to produce a second α3 expression vector, thefull-length α3 cDNA was excised from the pZeoα3 expression construct bydigestion with KpnI-NotI restriction enzymes. The double digested α3fragment was inserted in the expression vector pTargeT (Promega;Madison, Wis.), generating pTgTα3. This expression construct carries theG418 resistant gene for selection of resistant clones. Both expressionconstructs have been analyzed by restriction enzyme mapping and DNAsequencing.

[0152] Construction of Full-Length β3 Chain

[0153] Two cDNA fragments, Kal5-5c and Kal92-1, each cloned intoseparate pCR II vectors (Invitrogen), which together encode the entireβ3 chain of laminin-5 [SEQ ID NO:19], were received from Dr. Burgeson'slaboratory (4). The two fragments were cloned into a single vector toobtain the full-length β3 chain, plasmid PCRIIβ3.

[0154] Expression Vector Constructs for β3

[0155] The laminin β3 expression vector, pRCX3β3_(F), was constructedcontaining the full-length β3 chain obtained for pCRIIβ3 and the FLAGepitope added to the amino terminus [SEQ ID NO:17-18]. pRCX3 is a vectorderived from pRC/CMV (Invitrogen) and it contains a Geneticin resistantgene for selection with G418 sulfate, a BM 40 (SPARC) signal peptidesequence and the Flag peptide sequence in frame with convenient cloningsites

[0156] A second β3 expression vector was constructed by excising thecomplete laminin β3-flag peptide coding region from pRCX3β3_(F) plasmidand introducing it into pcDNA3.1/Zeo. This expression constructs carriesthe Zeocin resistant gene for selection.

[0157] Both β3-expression constructs have been analyzed by restrictionenzyme mapping and DNA sequencing.

[0158] Expression Vector Constructs for γ2

[0159] The full-length γ2 cDNA [SEQ ID NO:29] was excised from pVL1393γ2(received from Dr. Karl Tryggvason, Karolinska Institute, Sweden) bydigestion with BamH I-Xba I restriction enzymes. The double digested γ2fragment was inserted in the corresponding sites of the expressionvector pcDNA3.1/Zeo (Invitrogen), generating the pZeoγ2 expressionconstruct. This expression constructs carries the Zeocin resistant genefor selection.

[0160] Similarly, a BamH I-Not I full-length γ2 cDNA fragment was clonedinto the expression vector pTargeT (Promega), generating pTgTγ2. Thisexpression construct carries the G418 resistant gene for selection ofresistant clones.

[0161] Both expression constructs have been analyzed by restrictionenzyme mapping and DNA sequencing.

[0162] Sequence Analysis of Expression Constructs

[0163] The expression vector constructs have been sequenced and thereported gene sequences compared to the published sequences. Table 2shows a summary of the amino acid mismatches for the different lamininchains.

[0164] α3 chain: the reported sequence matched the published sequence.

[0165] β3 chain: several discrepancies with the published sequence werefound. Single and multiple base deletions and insertions are presentalong the sequence. These base changes generated some silent mutations,amino acid substitutions and insertion of amino acids. These changes donot cause early termination codons. Therefore, the β3 chain seems to beof “full-length” and the protein is being produced.

[0166] γ2 chain: This chain was reported to have 3 base changes creating3 amino acid substitutions. TABLE 2 Summary of amino acid differencesfrom those reported in the literature Laminin chain Amino acid change α3None β3 P, insertion at position 251-2 A₃₇₂—P₃₇₂ R₄₀₈R₄₀₉—Q₄₀₈G₄₀₉ R,insertion at position 421 P₅₈₄—R₅₈₄ A₇₉₆—G₇₉₆ R₈₉₄S₈₉₅E₈₉₆—S₈₉₄E₈₉₅A₈₉₆γ2 R₁₆₈—G₁₆₈ I₄₇₃—M₄₇₃ S₅₂₁—N₅₂₁

[0167] Transfection of Human Kidney 293 Cells

[0168] Wild type human kidney 293 cells were transfected with thedifferent expression constructs utilizing standard techniques. Twotransfection reagents were used, LIPOFECTAMINE™ from GIBCO (Rockville,Md.) and SUPERFECT™ from Qiagen (Valencia, Calif.). Experiments (seebelow) suggested that the 293 cells do not express detectable endogenouslaminin α3, β3, or γ2 chains

[0169] Briefly, both methods required mixing the transfection reagentwith the DNA of interest, incubating for a brief period at roomtemperature, and adding the mixture to the cells. The cells were splitthe previous day so they were at 50-80% confluency the day of thetransfection. The incubation with the DNA-reagent complexes wasconducted for 2-3 hours in serum free media for LIPOFECTAMINE™transfection or complete media for SUPERFECT™ transfection. After thisincubation period the media was replaced with fresh growth media and theincubation was continued until the selection process begins.

[0170] The selection process was carried out in DMEM F12/10% FBScontaining either Geneticin (G418 sulfate) at 400 μg/ml for selection ofG418 resistants, or Zeocin at 50 μg/ml for selection of Zeocinresistants. After splitting to selective media, the cells were fed everytwo days with fresh selective media, until cell foci were identified.Clones transfected with the three laminin chains and secreting r-laminin5 into the medium were selected with media containing both antibiotics.

[0171] Results

[0172] Media from human kidney 293 cells transfected with a singlelaminin chain were initially analyzed on Western blots usingchain-specific anti-laminin-5 antibodies. Cell fractions, as well as“whole” fractions containing cells plus any deposited “matrix-like”material obtained by scraping the cells into loading buffer, were alsoanalyzed. Western blot analysis of wild type 293 cell cultures showed nodetectable laminin α3, β3, or γ2 chain proteins.

[0173] The expression of single laminin chains following transfection isgenerally intracellular, except for a few β3 clones that appear to showβ3 chain reactivity in the media in Western blot analyses using theanti-FLAG antibody.

[0174] All clones showing FLAG antibody reactivity were verified by PCRto confirm the incorporation of the transfected gene. Analysis ofgenomic DNA preparations from such clones by PCR was done using lamininchain-specific primer pairs. The amplified products were compared topositive controls where the original expression constructs were used astemplates. Results are shown in Table 3. A few selected clones wereanalyzed by RT-PCR using the same laminin chain-specific primers andtotal RNA and/or mRNA preparations as templates. These results are alsoshown in Table 2.

[0175] Other data (not shown) demonstrated that the molecular sizes ofsome of the components of r-laminin 5 were different from those inpurified laminin 5. Particularly, the major component of the α3 chain inpurified laminin 5 was 165 kD, while the α3 band in r-laminin 5 migratedas two chains of 150 kD and 95 kD.

[0176] Identified co-transfected clones producing all three chains (asassessed by both genomic PCR and RT-PCR analysis), were further analyzedin a keratinocyte cell adhesion binding assay.

[0177] HFK cell adhesion assay for laminin-5. The method used measureslaminin-5 activity present in conditioned media from various clones. Anylaminin-5 present in the test media was trapped to a 96 well via ananti-laminin α3 antibody (C 25). Human foreskin keratinocytes (HFK) werelabeled fluorescently, added to the treated wells, and allowed to adherefor 30 minutes. Fluorescence was measured before and after washing withPBS. The % cell adhesion is equal to fraction of fluorescence retainedin the well. As controls, cells were pre-incubated with an anti-integrinα3β1 inhibitory antibody (P1B5)(α3β1 is the cell receptor for laminin5), or non-specific control antibody (SP2) before being added to thewells. Media controls (Keratinocyte growth media (“KGM”); or DMEM F12culture media (“medium”) were also used. The “α2_(F)” notation denotesculture medium from 293 cells transfected to express an unrelatedFLAG-containing protein.

[0178] The results, shown in Table 2 (last column) and in FIG. 1. Thefigure is labeled as follows: C5 and F10: conditioned culture media fromr-laminin-5 producing clones C5 and F10; *C6 and *F10: conditionedculture media collected earlier and kept refrigerated. These datademonstrated that media from several clones produced positive results inthe cell adhesion assay, indicating the r-laminin-5 produced by theseclones is biologically active. The activity was inhibited in thepresence of an integrin α3β1 antibody, demonstrating that the r-laminin5 is binding to the cells via the α3β1 integrin.

[0179] To assist in the purification of the heterotrimer r-laminin-5molecule, the laminin 3 chain was labeled with a ‘flag’ sequence at theamino terminus end. Media from clones transfected with all three chains,and shown to express all three chains, were passed through an anti-flagcolumn and eluted with excess flag peptide. The eluted fractions wereanalyzed by gel electrophoresis. The data demonstrate that r-laminin 5was produced and isolated. TABLE 3 Summary analysis of selected r-L5clones Western Blot PCR¹ RT-PCR² Adhesion Clone α3 β3 γ2 Flag α3 β3 γ2α3 β3 γ2 Assay A2-3 — nd nd + − + + − + + − A4-3 + + + + + + + + + + +A10-3 − nd + + − + − − + + − B1-6 nd nd nd + + + + + + + + C2-3 − nd + +− + + + + + − C5-7 nd nd nd + + + + nd + + − C6-3 + + + + + + + + + + +C10-3 − nd nd + − + + + + + − E1-3 − nd nd − − + − − + + − E2-3 − nd + +− + − + + + − E7-3 − nd − + − + − − + + − F10-5 nd nd nd + + + + + + + +

[0180] Several of the above clones were selected for further analysis. A1 liter culture from clone F10-5 was prepared, and r-laminin 5 waspurified using the methods described above. The r-laminin 5 was used inan HFK cell adhesion assay exactly as described above, except thatr-laminin 5 was coated directly onto the plate. The results arepresented in FIG. 2 and demonstrate that r-laminin 5 markedly increasesadhesion of HFK cells at all concentrations tested.

[0181] Electron Micrograph Analysis

[0182] Purified r-laminin 5 protein was diluted to 50 μg/ml and adjustedto 70% glycerol/30% 0.15M ammonium bicarbonate and rotary shadowed usingstandard techniques. FIG. 3 shows an 80,000× magnification field of (A)r-laminin 5; and (B) “native” laminin 5 (purified by BM165 monoclonalantibody affinity chromatography from SCC-25 (squamous cell carcinomacell line) conditioned medium). The bar represents 50 μm. These resultsdemonstrated that both the r-laminin 5 and the “native” purified laminin5 formed similar cross-shaped structures typical of laminins.

[0183] The present invention is not limited by the aforementionedparticular preferred embodiments. It will occur to those ordinarilyskilled in the art that various modifications may be made to thedisclosed preferred embodiments without diverting from the concept ofthe invention. All such modifications are intended to be within thescope of the present invention.

1 36 1 5280 DNA Homo sapiens CDS (18)..(5189) sig_peptide (18)..(110) 1taattaactg gttccgg atg cct cca gca gtg agg cgg tca gcc tgc agc 50 MetPro Pro Ala Val Arg Arg Ser Ala Cys Ser 1 5 10 atg gga tgg ctg tgg atcttt ggg gca gcc ctg ggg cag tgt ctg ggc 98 Met Gly Trp Leu Trp Ile PheGly Ala Ala Leu Gly Gln Cys Leu Gly 15 20 25 tac agt tca cag cag caa agggtg cca ttt ctt cag cct ccc ggt caa 146 Tyr Ser Ser Gln Gln Gln Arg ValPro Phe Leu Gln Pro Pro Gly Gln 30 35 40 agt caa ctg caa gcg agt tat gtggag ttt aga ccc agc cag ggt tgt 194 Ser Gln Leu Gln Ala Ser Tyr Val GluPhe Arg Pro Ser Gln Gly Cys 45 50 55 agc cct gga tac tat cgg gat cat aaaggc ttg tat acc gga cgg tgt 242 Ser Pro Gly Tyr Tyr Arg Asp His Lys GlyLeu Tyr Thr Gly Arg Cys 60 65 70 75 gtt ccc tgc aat tgc aac gga cat tcaaat caa tgc cag gat ggc tca 290 Val Pro Cys Asn Cys Asn Gly His Ser AsnGln Cys Gln Asp Gly Ser 80 85 90 ggc ata tgt gtt aac tgt cag cac aac accgcg gga gag cac tgt gaa 338 Gly Ile Cys Val Asn Cys Gln His Asn Thr AlaGly Glu His Cys Glu 95 100 105 cgc tgc cag gag ggc tac tat ggc aac gccgtc cac gga tcc tgc agg 386 Arg Cys Gln Glu Gly Tyr Tyr Gly Asn Ala ValHis Gly Ser Cys Arg 110 115 120 gcc tgc cca tgt cct cac act aac agc tttgcc act ggc tgt gtg gtg 434 Ala Cys Pro Cys Pro His Thr Asn Ser Phe AlaThr Gly Cys Val Val 125 130 135 aat ggg gga gac gtg cgg tgc tcc tgc aaagct ggg tac aca gga aca 482 Asn Gly Gly Asp Val Arg Cys Ser Cys Lys AlaGly Tyr Thr Gly Thr 140 145 150 155 cag tgt gaa agg tgt gca ccg gga tatttc ggg aat ccc cag aaa ttc 530 Gln Cys Glu Arg Cys Ala Pro Gly Tyr PheGly Asn Pro Gln Lys Phe 160 165 170 gga ggt agc tgc caa cca tgc agt tgtaac agc aat ggc cag ctg ggc 578 Gly Gly Ser Cys Gln Pro Cys Ser Cys AsnSer Asn Gly Gln Leu Gly 175 180 185 agc tgt cat ccc ctg act gga gac tgcata aac caa gaa ccc aaa gat 626 Ser Cys His Pro Leu Thr Gly Asp Cys IleAsn Gln Glu Pro Lys Asp 190 195 200 agc agc cct gca gaa gaa tgt gat gattgc gac agc tgt gtg atg acc 674 Ser Ser Pro Ala Glu Glu Cys Asp Asp CysAsp Ser Cys Val Met Thr 205 210 215 ctc ctg aac gac ctg gcc acc atg ggcgag cag ctc cgc ctg gtc aag 722 Leu Leu Asn Asp Leu Ala Thr Met Gly GluGln Leu Arg Leu Val Lys 220 225 230 235 tct cag ctg cag ggc ctg agt gccagc gca ggg ctt ctg gag cag atg 770 Ser Gln Leu Gln Gly Leu Ser Ala SerAla Gly Leu Leu Glu Gln Met 240 245 250 agg cac atg gag acc cag gcc aaggac ctg agg aat cag ttg ctc aac 818 Arg His Met Glu Thr Gln Ala Lys AspLeu Arg Asn Gln Leu Leu Asn 255 260 265 tac cgt tct gcc att tca aat catgga tca aaa ata gaa ggc ctg gaa 866 Tyr Arg Ser Ala Ile Ser Asn His GlySer Lys Ile Glu Gly Leu Glu 270 275 280 aga gaa ctg act gat ttg aat caagaa ttt gag act tta caa gaa aag 914 Arg Glu Leu Thr Asp Leu Asn Gln GluPhe Glu Thr Leu Gln Glu Lys 285 290 295 gct caa gta aat tcc aga aaa gcacaa aca tta aac aac aat gtt aat 962 Ala Gln Val Asn Ser Arg Lys Ala GlnThr Leu Asn Asn Asn Val Asn 300 305 310 315 cgg gca aca caa agc gca aaagaa cta gat gtg aag att aaa aat gtc 1010 Arg Ala Thr Gln Ser Ala Lys GluLeu Asp Val Lys Ile Lys Asn Val 320 325 330 atc cgg aat gtg cac att ctttta aag cag atc tct ggg aca gat gga 1058 Ile Arg Asn Val His Ile Leu LeuLys Gln Ile Ser Gly Thr Asp Gly 335 340 345 gag gga aac aac gtg cct tcaggt gac ttt tcc aga gag tgg gct gaa 1106 Glu Gly Asn Asn Val Pro Ser GlyAsp Phe Ser Arg Glu Trp Ala Glu 350 355 360 gcc cag cgc atg atg agg gaactg cgg aac agg aac ttt gga aag cac 1154 Ala Gln Arg Met Met Arg Glu LeuArg Asn Arg Asn Phe Gly Lys His 365 370 375 ctc aga gaa gca gaa gct gataaa agg gag tcg cag ctc ttg ctg aac 1202 Leu Arg Glu Ala Glu Ala Asp LysArg Glu Ser Gln Leu Leu Leu Asn 380 385 390 395 cgg ata agg acc tgg cagaaa acc cac cag ggg gag aac aat ggg ctt 1250 Arg Ile Arg Thr Trp Gln LysThr His Gln Gly Glu Asn Asn Gly Leu 400 405 410 gct aac agt atc cgg gattct tta aat gaa tac gaa gcc aaa ctc agt 1298 Ala Asn Ser Ile Arg Asp SerLeu Asn Glu Tyr Glu Ala Lys Leu Ser 415 420 425 gac ctt cgt gct cgg ctgcag gag gca gct gcc caa gcc aag cag gca 1346 Asp Leu Arg Ala Arg Leu GlnGlu Ala Ala Ala Gln Ala Lys Gln Ala 430 435 440 aat ggc ttg aac caa gaaaac gag aga gct ttg gga gcc att cag aga 1394 Asn Gly Leu Asn Gln Glu AsnGlu Arg Ala Leu Gly Ala Ile Gln Arg 445 450 455 caa gtg aaa gaa ata aattcc ctg cag agt gat ttc acc aag tat cta 1442 Gln Val Lys Glu Ile Asn SerLeu Gln Ser Asp Phe Thr Lys Tyr Leu 460 465 470 475 acc act gca gac tcatct ttg ttg caa acc aac att gcg ctg cag ctg 1490 Thr Thr Ala Asp Ser SerLeu Leu Gln Thr Asn Ile Ala Leu Gln Leu 480 485 490 atg gag aaa agc cagaag gaa tat gaa aaa tta gct gcc agt tta aat 1538 Met Glu Lys Ser Gln LysGlu Tyr Glu Lys Leu Ala Ala Ser Leu Asn 495 500 505 gaa gca aga caa gaacta agt gac aaa gta aga gaa ctt tcc aga tct 1586 Glu Ala Arg Gln Glu LeuSer Asp Lys Val Arg Glu Leu Ser Arg Ser 510 515 520 gct ggc aaa aca tccctt gtg gag gag gca gaa aag cac gcg cgg tcc 1634 Ala Gly Lys Thr Ser LeuVal Glu Glu Ala Glu Lys His Ala Arg Ser 525 530 535 tta caa gag ctg gcaaag cag ctg gaa gag atc aag aga aac gcc agc 1682 Leu Gln Glu Leu Ala LysGln Leu Glu Glu Ile Lys Arg Asn Ala Ser 540 545 550 555 ggg gat gag ctggtg cgc tgt gct gtg gat gcc gcc acc gcc tac gag 1730 Gly Asp Glu Leu ValArg Cys Ala Val Asp Ala Ala Thr Ala Tyr Glu 560 565 570 aac atc ctc aatgcc atc aaa gcg gcc gag gac gca gcc aac agg gct 1778 Asn Ile Leu Asn AlaIle Lys Ala Ala Glu Asp Ala Ala Asn Arg Ala 575 580 585 gcc agt gca tctgaa tct gcc ctc cag aca gtg ata aag gaa gat ctg 1826 Ala Ser Ala Ser GluSer Ala Leu Gln Thr Val Ile Lys Glu Asp Leu 590 595 600 cca aga aaa gctaaa acc ctg agt tcc aac agt gat aaa ctg tta aat 1874 Pro Arg Lys Ala LysThr Leu Ser Ser Asn Ser Asp Lys Leu Leu Asn 605 610 615 gaa gcc aag atgaca caa aag aag cta aag caa gaa gtc agt cca gct 1922 Glu Ala Lys Met ThrGln Lys Lys Leu Lys Gln Glu Val Ser Pro Ala 620 625 630 635 ctc aac aaccta cag caa acc ctg aat att gtg aca gtt cag aaa gaa 1970 Leu Asn Asn LeuGln Gln Thr Leu Asn Ile Val Thr Val Gln Lys Glu 640 645 650 gtg ata gacacc aat ctc aca act ctc cga gat ggt ctt cat ggg ata 2018 Val Ile Asp ThrAsn Leu Thr Thr Leu Arg Asp Gly Leu His Gly Ile 655 660 665 cag aga ggtgat att gat gct atg atc agt agt gca aag agc atg gtc 2066 Gln Arg Gly AspIle Asp Ala Met Ile Ser Ser Ala Lys Ser Met Val 670 675 680 aga aag gccaac gac atc aca gat gag gtt ctg gat ggg ctc aac ccc 2114 Arg Lys Ala AsnAsp Ile Thr Asp Glu Val Leu Asp Gly Leu Asn Pro 685 690 695 atc cag acagat gtg gaa aga att aag gac acc tat ggg agg aca cag 2162 Ile Gln Thr AspVal Glu Arg Ile Lys Asp Thr Tyr Gly Arg Thr Gln 700 705 710 715 aac gaagac ttc aaa aag gct ctg act gat gca gat aac tcg gtg aat 2210 Asn Glu AspPhe Lys Lys Ala Leu Thr Asp Ala Asp Asn Ser Val Asn 720 725 730 aag ttaacc aac aaa cta cct gat ctt tgg cgc aag att gaa agt atc 2258 Lys Leu ThrAsn Lys Leu Pro Asp Leu Trp Arg Lys Ile Glu Ser Ile 735 740 745 aac caacag ctg ttg ccc ttg gga aac atc tct gac aac atg gac aga 2306 Asn Gln GlnLeu Leu Pro Leu Gly Asn Ile Ser Asp Asn Met Asp Arg 750 755 760 ata cgagaa cta att cag cag gcc aga gat gct gcc agt aag gtt gct 2354 Ile Arg GluLeu Ile Gln Gln Ala Arg Asp Ala Ala Ser Lys Val Ala 765 770 775 gtc cccatg agg ttc aat ggt aaa tct gga gtc gaa gtc cga ctg cca 2402 Val Pro MetArg Phe Asn Gly Lys Ser Gly Val Glu Val Arg Leu Pro 780 785 790 795 aatgac ctg gaa gat ttg aaa gga tat aca tct ctg tcc ttg ttt ctc 2450 Asn AspLeu Glu Asp Leu Lys Gly Tyr Thr Ser Leu Ser Leu Phe Leu 800 805 810 caaagg ccc aac tca aga gaa aat ggg ggt act gag aat atg ttt gtg 2498 Gln ArgPro Asn Ser Arg Glu Asn Gly Gly Thr Glu Asn Met Phe Val 815 820 825 atgtac ctt gga aat aaa gat gcc tcc cgg gac tac atc ggc atg gca 2546 Met TyrLeu Gly Asn Lys Asp Ala Ser Arg Asp Tyr Ile Gly Met Ala 830 835 840 gttgtg gat ggc cag ctc acc tgt gtc tac aac ctg ggg gac cgt gag 2594 Val ValAsp Gly Gln Leu Thr Cys Val Tyr Asn Leu Gly Asp Arg Glu 845 850 855 gctgaa ctc caa gtg gac cag atc ttg acc aag agt gag act aag gag 2642 Ala GluLeu Gln Val Asp Gln Ile Leu Thr Lys Ser Glu Thr Lys Glu 860 865 870 875gca gtt atg gat cgg gtg aaa ttt cag aga att tat cag ttt gca agg 2690 AlaVal Met Asp Arg Val Lys Phe Gln Arg Ile Tyr Gln Phe Ala Arg 880 885 890ctt aat tac acc aaa gga gcc aca tcc agt aaa cca gaa aca ccc gga 2738 LeuAsn Tyr Thr Lys Gly Ala Thr Ser Ser Lys Pro Glu Thr Pro Gly 895 900 905gtc tat gac atg gat ggt aga aat agc aat aca ctc ctt aat ttg gat 2786 ValTyr Asp Met Asp Gly Arg Asn Ser Asn Thr Leu Leu Asn Leu Asp 910 915 920cct gaa aat gtt gta ttt tat gtt gga ggt tac cca cct gat ttt aaa 2834 ProGlu Asn Val Val Phe Tyr Val Gly Gly Tyr Pro Pro Asp Phe Lys 925 930 935ctt ccc agt cga cta agt ttc cct cca tac aaa ggt tgt att gaa tta 2882 LeuPro Ser Arg Leu Ser Phe Pro Pro Tyr Lys Gly Cys Ile Glu Leu 940 945 950955 gat gac ctc aat gaa aat gtt ctg agc ttg tac aac ttc aaa aaa aca 2930Asp Asp Leu Asn Glu Asn Val Leu Ser Leu Tyr Asn Phe Lys Lys Thr 960 965970 ttc aat ctc aac aca act gaa gtg gag cct tgt aga agg agg aag gaa 2978Phe Asn Leu Asn Thr Thr Glu Val Glu Pro Cys Arg Arg Arg Lys Glu 975 980985 gag tca gac aaa aat tat ttt gaa ggt acg ggc tat gct cga gtt cca 3026Glu Ser Asp Lys Asn Tyr Phe Glu Gly Thr Gly Tyr Ala Arg Val Pro 990 9951000 act caa cca cat gct ccc atc cca acc ttt gga cag aca att cag acc3074 Thr Gln Pro His Ala Pro Ile Pro Thr Phe Gly Gln Thr Ile Gln Thr1005 1010 1015 acc gtg gat aga ggc ttg ctg ttc ttt gca gaa aac ggg gatcgc ttc 3122 Thr Val Asp Arg Gly Leu Leu Phe Phe Ala Glu Asn Gly Asp ArgPhe 1020 1025 1030 1035 ata tct cta aat ata gaa gat ggc aag ctc atg gtgaga tac aaa ctg 3170 Ile Ser Leu Asn Ile Glu Asp Gly Lys Leu Met Val ArgTyr Lys Leu 1040 1045 1050 aat tca gag cta cca aaa gag aga gga gtt ggagac gcc ata aac aac 3218 Asn Ser Glu Leu Pro Lys Glu Arg Gly Val Gly AspAla Ile Asn Asn 1055 1060 1065 ggc aga gac cat tcg att cag atc aaa attgga aaa ctc caa aag cgt 3266 Gly Arg Asp His Ser Ile Gln Ile Lys Ile GlyLys Leu Gln Lys Arg 1070 1075 1080 atg tgg ata aat gtg gac gtt caa aacact ata att gat ggt gaa gta 3314 Met Trp Ile Asn Val Asp Val Gln Asn ThrIle Ile Asp Gly Glu Val 1085 1090 1095 ttt gat ttc agc aca tat tat ctggga gga att cca att gca atc agg 3362 Phe Asp Phe Ser Thr Tyr Tyr Leu GlyGly Ile Pro Ile Ala Ile Arg 1100 1105 1110 1115 gaa aga ttt aac att tctacg cct gct ttc cga ggc tgc atg aaa aat 3410 Glu Arg Phe Asn Ile Ser ThrPro Ala Phe Arg Gly Cys Met Lys Asn 1120 1125 1130 ttg aag aaa acc agtggt gtc gtt aga ttg aat gat act gtg gga gta 3458 Leu Lys Lys Thr Ser GlyVal Val Arg Leu Asn Asp Thr Val Gly Val 1135 1140 1145 acc aaa aag tgctcg gaa gac tgg aag ctt gtg cga tct gcc tca ttc 3506 Thr Lys Lys Cys SerGlu Asp Trp Lys Leu Val Arg Ser Ala Ser Phe 1150 1155 1160 tcc aga ggagga caa ttg agt ttc act gat ttg ggc tta cca cct act 3554 Ser Arg Gly GlyGln Leu Ser Phe Thr Asp Leu Gly Leu Pro Pro Thr 1165 1170 1175 gac cacctc cag gcc tca ttt gga ttt cag acc ttt caa ccc agt ggc 3602 Asp His LeuGln Ala Ser Phe Gly Phe Gln Thr Phe Gln Pro Ser Gly 1180 1185 1190 1195ata tta tta gat cat cag aca tgg aca agg aac ctg cag gtc act ctg 3650 IleLeu Leu Asp His Gln Thr Trp Thr Arg Asn Leu Gln Val Thr Leu 1200 12051210 gaa gat ggt tac att gaa ttg agc acc agc gat agc ggc ggc cca att3698 Glu Asp Gly Tyr Ile Glu Leu Ser Thr Ser Asp Ser Gly Gly Pro Ile1215 1220 1225 ttt aaa tct cca cag acg tat atg gat ggt tta ctg cat tatgta tct 3746 Phe Lys Ser Pro Gln Thr Tyr Met Asp Gly Leu Leu His Tyr ValSer 1230 1235 1240 gta ata agc gac aac tct gga cta cgg ctt ctc atc gatgac cag ctt 3794 Val Ile Ser Asp Asn Ser Gly Leu Arg Leu Leu Ile Asp AspGln Leu 1245 1250 1255 ctg aga aat agc aaa agg cta aaa cac att tca agttcc cgg cag tct 3842 Leu Arg Asn Ser Lys Arg Leu Lys His Ile Ser Ser SerArg Gln Ser 1260 1265 1270 1275 ctg cgt ctg ggc ggg agc aat ttt gag ggttgt att agc aat gtt ttt 3890 Leu Arg Leu Gly Gly Ser Asn Phe Glu Gly CysIle Ser Asn Val Phe 1280 1285 1290 gtc cag agg tta tca ctg agt cct gaagtc cta gat ttg acc agt aac 3938 Val Gln Arg Leu Ser Leu Ser Pro Glu ValLeu Asp Leu Thr Ser Asn 1295 1300 1305 tct ctc aag aga gat gtg tcc ctggga ggc tgc agt tta aac aaa cca 3986 Ser Leu Lys Arg Asp Val Ser Leu GlyGly Cys Ser Leu Asn Lys Pro 1310 1315 1320 cct ttt cta atg ttg ctt aaaggt tct acc agg ttt aac aag acc aag 4034 Pro Phe Leu Met Leu Leu Lys GlySer Thr Arg Phe Asn Lys Thr Lys 1325 1330 1335 act ttt cgt atc aac cagctg ttg cag gac aca cca gtg gcc tcc cca 4082 Thr Phe Arg Ile Asn Gln LeuLeu Gln Asp Thr Pro Val Ala Ser Pro 1340 1345 1350 1355 agg agc gtg aaggtg tgg caa gat gct tgc tca cca ctt ccc aag acc 4130 Arg Ser Val Lys ValTrp Gln Asp Ala Cys Ser Pro Leu Pro Lys Thr 1360 1365 1370 cag gcc aatcat gga gcc ctc cag ttt ggg gac att ccc acc agc cac 4178 Gln Ala Asn HisGly Ala Leu Gln Phe Gly Asp Ile Pro Thr Ser His 1375 1380 1385 ttg ctattc aag ctt cct cag gag ctg ctg aaa ccc agg tca cag ttt 4226 Leu Leu PheLys Leu Pro Gln Glu Leu Leu Lys Pro Arg Ser Gln Phe 1390 1395 1400 gctgtg gac atg cag aca aca tcc tcc aga gga ctg gtg ttt cac acg 4274 Ala ValAsp Met Gln Thr Thr Ser Ser Arg Gly Leu Val Phe His Thr 1405 1410 1415ggc act aag aac tcc ttt atg gct ctt tat ctt tca aaa gga cgt ctg 4322 GlyThr Lys Asn Ser Phe Met Ala Leu Tyr Leu Ser Lys Gly Arg Leu 1420 14251430 1435 gtc ttt gca ctg ggg aca gat ggg aaa aaa ttg agg atc aaa agcaag 4370 Val Phe Ala Leu Gly Thr Asp Gly Lys Lys Leu Arg Ile Lys Ser Lys1440 1445 1450 gag aaa tgc aat gat ggg aaa tgg cac acg gtg gtg ttt ggccat gat 4418 Glu Lys Cys Asn Asp Gly Lys Trp His Thr Val Val Phe Gly HisAsp 1455 1460 1465 ggg gaa aag ggg cgc ttg gtt gtg gat gga ctg agg gcccgg gag gga 4466 Gly Glu Lys Gly Arg Leu Val Val Asp Gly Leu Arg Ala ArgGlu Gly 1470 1475 1480 agt ttg cct gga aac tcc acc atc agc atc aga gcgcca gtt tac ctg 4514 Ser Leu Pro Gly Asn Ser Thr Ile Ser Ile Arg Ala ProVal Tyr Leu 1485 1490 1495 gga tca cct cca tca ggg aaa cca aag agc ctcccc aca aac agc ttt 4562 Gly Ser Pro Pro Ser Gly Lys Pro Lys Ser Leu ProThr Asn Ser Phe 1500 1505 1510 1515 gtg gga tgc ctg aag aac ttt cag ctggat tca aaa ccc ttg tat acc 4610 Val Gly Cys Leu Lys Asn Phe Gln Leu AspSer Lys Pro Leu Tyr Thr 1520 1525 1530 cct tct tca agc ttc ggg gtg tcttcc tgc ttg ggt ggt cct ttg gag 4658 Pro Ser Ser Ser Phe Gly Val Ser SerCys Leu Gly Gly Pro Leu Glu 1535 1540 1545 aaa ggc att tat ttc tct gaagaa gga ggt cat gtc gtc ttg gct cac 4706 Lys Gly Ile Tyr Phe Ser Glu GluGly Gly His Val Val Leu Ala His 1550 1555 1560 tct gta ttg ttg ggg ccagaa ttt aag ctt gtt ttc agc atc cgc cca 4754 Ser Val Leu Leu Gly Pro GluPhe Lys Leu Val Phe Ser Ile Arg Pro 1565 1570 1575 aga agt ctc act gggatc cta ata cac atc gga agt cag ccc ggg aag 4802 Arg Ser Leu Thr Gly IleLeu Ile His Ile Gly Ser Gln Pro Gly Lys 1580 1585 1590 1595 cac tta tgtgtt tac ctg gag gca gga aag gtc acg gcc tct atg gac 4850 His Leu Cys ValTyr Leu Glu Ala Gly Lys Val Thr Ala Ser Met Asp 1600 1605 1610 agt ggggca ggt ggg acc tca acg tcg gtc aca cca aag cag tct ctg 4898 Ser Gly AlaGly Gly Thr Ser Thr Ser Val Thr Pro Lys Gln Ser Leu 1615 1620 1625 tgtgat gga cag tgg cac tcg gtg gca gtc acc ata aaa caa cac atc 4946 Cys AspGly Gln Trp His Ser Val Ala Val Thr Ile Lys Gln His Ile 1630 1635 1640ctg cac ctg gaa ctg gac aca gac agt agc tac aca gct gga cag atc 4994 LeuHis Leu Glu Leu Asp Thr Asp Ser Ser Tyr Thr Ala Gly Gln Ile 1645 16501655 ccc ttc cca cct gcc agc act caa gag cca cta cac ctt gga ggt gct5042 Pro Phe Pro Pro Ala Ser Thr Gln Glu Pro Leu His Leu Gly Gly Ala1660 1665 1670 1675 cca gcc aat ttg acg aca ctg agg atc cct gtg tgg aaatca ttc ttt 5090 Pro Ala Asn Leu Thr Thr Leu Arg Ile Pro Val Trp Lys SerPhe Phe 1680 1685 1690 ggc tgt ctg agg aat att cat gtc aat cac atc cctgtc cct gtc act 5138 Gly Cys Leu Arg Asn Ile His Val Asn His Ile Pro ValPro Val Thr 1695 1700 1705 gaa gcc ttg gaa gtc cag ggg cct gtc agt ctgaat ggt tgt cct gac 5186 Glu Ala Leu Glu Val Gln Gly Pro Val Ser Leu AsnGly Cys Pro Asp 1710 1715 1720 cag taacccaagc ctatttcaca gcaaggaaattcaccttcaa aagcactgat 5239 Gln tacccaatgc acctccctcc ccagctcgagatcattcttc a 5280 2 1724 PRT Homo sapiens 2 Met Pro Pro Ala Val Arg ArgSer Ala Cys Ser Met Gly Trp Leu Trp 1 5 10 15 Ile Phe Gly Ala Ala LeuGly Gln Cys Leu Gly Tyr Ser Ser Gln Gln 20 25 30 Gln Arg Val Pro Phe LeuGln Pro Pro Gly Gln Ser Gln Leu Gln Ala 35 40 45 Ser Tyr Val Glu Phe ArgPro Ser Gln Gly Cys Ser Pro Gly Tyr Tyr 50 55 60 Arg Asp His Lys Gly LeuTyr Thr Gly Arg Cys Val Pro Cys Asn Cys 65 70 75 80 Asn Gly His Ser AsnGln Cys Gln Asp Gly Ser Gly Ile Cys Val Asn 85 90 95 Cys Gln His Asn ThrAla Gly Glu His Cys Glu Arg Cys Gln Glu Gly 100 105 110 Tyr Tyr Gly AsnAla Val His Gly Ser Cys Arg Ala Cys Pro Cys Pro 115 120 125 His Thr AsnSer Phe Ala Thr Gly Cys Val Val Asn Gly Gly Asp Val 130 135 140 Arg CysSer Cys Lys Ala Gly Tyr Thr Gly Thr Gln Cys Glu Arg Cys 145 150 155 160Ala Pro Gly Tyr Phe Gly Asn Pro Gln Lys Phe Gly Gly Ser Cys Gln 165 170175 Pro Cys Ser Cys Asn Ser Asn Gly Gln Leu Gly Ser Cys His Pro Leu 180185 190 Thr Gly Asp Cys Ile Asn Gln Glu Pro Lys Asp Ser Ser Pro Ala Glu195 200 205 Glu Cys Asp Asp Cys Asp Ser Cys Val Met Thr Leu Leu Asn AspLeu 210 215 220 Ala Thr Met Gly Glu Gln Leu Arg Leu Val Lys Ser Gln LeuGln Gly 225 230 235 240 Leu Ser Ala Ser Ala Gly Leu Leu Glu Gln Met ArgHis Met Glu Thr 245 250 255 Gln Ala Lys Asp Leu Arg Asn Gln Leu Leu AsnTyr Arg Ser Ala Ile 260 265 270 Ser Asn His Gly Ser Lys Ile Glu Gly LeuGlu Arg Glu Leu Thr Asp 275 280 285 Leu Asn Gln Glu Phe Glu Thr Leu GlnGlu Lys Ala Gln Val Asn Ser 290 295 300 Arg Lys Ala Gln Thr Leu Asn AsnAsn Val Asn Arg Ala Thr Gln Ser 305 310 315 320 Ala Lys Glu Leu Asp ValLys Ile Lys Asn Val Ile Arg Asn Val His 325 330 335 Ile Leu Leu Lys GlnIle Ser Gly Thr Asp Gly Glu Gly Asn Asn Val 340 345 350 Pro Ser Gly AspPhe Ser Arg Glu Trp Ala Glu Ala Gln Arg Met Met 355 360 365 Arg Glu LeuArg Asn Arg Asn Phe Gly Lys His Leu Arg Glu Ala Glu 370 375 380 Ala AspLys Arg Glu Ser Gln Leu Leu Leu Asn Arg Ile Arg Thr Trp 385 390 395 400Gln Lys Thr His Gln Gly Glu Asn Asn Gly Leu Ala Asn Ser Ile Arg 405 410415 Asp Ser Leu Asn Glu Tyr Glu Ala Lys Leu Ser Asp Leu Arg Ala Arg 420425 430 Leu Gln Glu Ala Ala Ala Gln Ala Lys Gln Ala Asn Gly Leu Asn Gln435 440 445 Glu Asn Glu Arg Ala Leu Gly Ala Ile Gln Arg Gln Val Lys GluIle 450 455 460 Asn Ser Leu Gln Ser Asp Phe Thr Lys Tyr Leu Thr Thr AlaAsp Ser 465 470 475 480 Ser Leu Leu Gln Thr Asn Ile Ala Leu Gln Leu MetGlu Lys Ser Gln 485 490 495 Lys Glu Tyr Glu Lys Leu Ala Ala Ser Leu AsnGlu Ala Arg Gln Glu 500 505 510 Leu Ser Asp Lys Val Arg Glu Leu Ser ArgSer Ala Gly Lys Thr Ser 515 520 525 Leu Val Glu Glu Ala Glu Lys His AlaArg Ser Leu Gln Glu Leu Ala 530 535 540 Lys Gln Leu Glu Glu Ile Lys ArgAsn Ala Ser Gly Asp Glu Leu Val 545 550 555 560 Arg Cys Ala Val Asp AlaAla Thr Ala Tyr Glu Asn Ile Leu Asn Ala 565 570 575 Ile Lys Ala Ala GluAsp Ala Ala Asn Arg Ala Ala Ser Ala Ser Glu 580 585 590 Ser Ala Leu GlnThr Val Ile Lys Glu Asp Leu Pro Arg Lys Ala Lys 595 600 605 Thr Leu SerSer Asn Ser Asp Lys Leu Leu Asn Glu Ala Lys Met Thr 610 615 620 Gln LysLys Leu Lys Gln Glu Val Ser Pro Ala Leu Asn Asn Leu Gln 625 630 635 640Gln Thr Leu Asn Ile Val Thr Val Gln Lys Glu Val Ile Asp Thr Asn 645 650655 Leu Thr Thr Leu Arg Asp Gly Leu His Gly Ile Gln Arg Gly Asp Ile 660665 670 Asp Ala Met Ile Ser Ser Ala Lys Ser Met Val Arg Lys Ala Asn Asp675 680 685 Ile Thr Asp Glu Val Leu Asp Gly Leu Asn Pro Ile Gln Thr AspVal 690 695 700 Glu Arg Ile Lys Asp Thr Tyr Gly Arg Thr Gln Asn Glu AspPhe Lys 705 710 715 720 Lys Ala Leu Thr Asp Ala Asp Asn Ser Val Asn LysLeu Thr Asn Lys 725 730 735 Leu Pro Asp Leu Trp Arg Lys Ile Glu Ser IleAsn Gln Gln Leu Leu 740 745 750 Pro Leu Gly Asn Ile Ser Asp Asn Met AspArg Ile Arg Glu Leu Ile 755 760 765 Gln Gln Ala Arg Asp Ala Ala Ser LysVal Ala Val Pro Met Arg Phe 770 775 780 Asn Gly Lys Ser Gly Val Glu ValArg Leu Pro Asn Asp Leu Glu Asp 785 790 795 800 Leu Lys Gly Tyr Thr SerLeu Ser Leu Phe Leu Gln Arg Pro Asn Ser 805 810 815 Arg Glu Asn Gly GlyThr Glu Asn Met Phe Val Met Tyr Leu Gly Asn 820 825 830 Lys Asp Ala SerArg Asp Tyr Ile Gly Met Ala Val Val Asp Gly Gln 835 840 845 Leu Thr CysVal Tyr Asn Leu Gly Asp Arg Glu Ala Glu Leu Gln Val 850 855 860 Asp GlnIle Leu Thr Lys Ser Glu Thr Lys Glu Ala Val Met Asp Arg 865 870 875 880Val Lys Phe Gln Arg Ile Tyr Gln Phe Ala Arg Leu Asn Tyr Thr Lys 885 890895 Gly Ala Thr Ser Ser Lys Pro Glu Thr Pro Gly Val Tyr Asp Met Asp 900905 910 Gly Arg Asn Ser Asn Thr Leu Leu Asn Leu Asp Pro Glu Asn Val Val915 920 925 Phe Tyr Val Gly Gly Tyr Pro Pro Asp Phe Lys Leu Pro Ser ArgLeu 930 935 940 Ser Phe Pro Pro Tyr Lys Gly Cys Ile Glu Leu Asp Asp LeuAsn Glu 945 950 955 960 Asn Val Leu Ser Leu Tyr Asn Phe Lys Lys Thr PheAsn Leu Asn Thr 965 970 975 Thr Glu Val Glu Pro Cys Arg Arg Arg Lys GluGlu Ser Asp Lys Asn 980 985 990 Tyr Phe Glu Gly Thr Gly Tyr Ala Arg ValPro Thr Gln Pro His Ala 995 1000 1005 Pro Ile Pro Thr Phe Gly Gln ThrIle Gln Thr Thr Val Asp Arg Gly 1010 1015 1020 Leu Leu Phe Phe Ala GluAsn Gly Asp Arg Phe Ile Ser Leu Asn Ile 1025 1030 1035 1040 Glu Asp GlyLys Leu Met Val Arg Tyr Lys Leu Asn Ser Glu Leu Pro 1045 1050 1055 LysGlu Arg Gly Val Gly Asp Ala Ile Asn Asn Gly Arg Asp His Ser 1060 10651070 Ile Gln Ile Lys Ile Gly Lys Leu Gln Lys Arg Met Trp Ile Asn Val1075 1080 1085 Asp Val Gln Asn Thr Ile Ile Asp Gly Glu Val Phe Asp PheSer Thr 1090 1095 1100 Tyr Tyr Leu Gly Gly Ile Pro Ile Ala Ile Arg GluArg Phe Asn Ile 1105 1110 1115 1120 Ser Thr Pro Ala Phe Arg Gly Cys MetLys Asn Leu Lys Lys Thr Ser 1125 1130 1135 Gly Val Val Arg Leu Asn AspThr Val Gly Val Thr Lys Lys Cys Ser 1140 1145 1150 Glu Asp Trp Lys LeuVal Arg Ser Ala Ser Phe Ser Arg Gly Gly Gln 1155 1160 1165 Leu Ser PheThr Asp Leu Gly Leu Pro Pro Thr Asp His Leu Gln Ala 1170 1175 1180 SerPhe Gly Phe Gln Thr Phe Gln Pro Ser Gly Ile Leu Leu Asp His 1185 11901195 1200 Gln Thr Trp Thr Arg Asn Leu Gln Val Thr Leu Glu Asp Gly TyrIle 1205 1210 1215 Glu Leu Ser Thr Ser Asp Ser Gly Gly Pro Ile Phe LysSer Pro Gln 1220 1225 1230 Thr Tyr Met Asp Gly Leu Leu His Tyr Val SerVal Ile Ser Asp Asn 1235 1240 1245 Ser Gly Leu Arg Leu Leu Ile Asp AspGln Leu Leu Arg Asn Ser Lys 1250 1255 1260 Arg Leu Lys His Ile Ser SerSer Arg Gln Ser Leu Arg Leu Gly Gly 1265 1270 1275 1280 Ser Asn Phe GluGly Cys Ile Ser Asn Val Phe Val Gln Arg Leu Ser 1285 1290 1295 Leu SerPro Glu Val Leu Asp Leu Thr Ser Asn Ser Leu Lys Arg Asp 1300 1305 1310Val Ser Leu Gly Gly Cys Ser Leu Asn Lys Pro Pro Phe Leu Met Leu 13151320 1325 Leu Lys Gly Ser Thr Arg Phe Asn Lys Thr Lys Thr Phe Arg IleAsn 1330 1335 1340 Gln Leu Leu Gln Asp Thr Pro Val Ala Ser Pro Arg SerVal Lys Val 1345 1350 1355 1360 Trp Gln Asp Ala Cys Ser Pro Leu Pro LysThr Gln Ala Asn His Gly 1365 1370 1375 Ala Leu Gln Phe Gly Asp Ile ProThr Ser His Leu Leu Phe Lys Leu 1380 1385 1390 Pro Gln Glu Leu Leu LysPro Arg Ser Gln Phe Ala Val Asp Met Gln 1395 1400 1405 Thr Thr Ser SerArg Gly Leu Val Phe His Thr Gly Thr Lys Asn Ser 1410 1415 1420 Phe MetAla Leu Tyr Leu Ser Lys Gly Arg Leu Val Phe Ala Leu Gly 1425 1430 14351440 Thr Asp Gly Lys Lys Leu Arg Ile Lys Ser Lys Glu Lys Cys Asn Asp1445 1450 1455 Gly Lys Trp His Thr Val Val Phe Gly His Asp Gly Glu LysGly Arg 1460 1465 1470 Leu Val Val Asp Gly Leu Arg Ala Arg Glu Gly SerLeu Pro Gly Asn 1475 1480 1485 Ser Thr Ile Ser Ile Arg Ala Pro Val TyrLeu Gly Ser Pro Pro Ser 1490 1495 1500 Gly Lys Pro Lys Ser Leu Pro ThrAsn Ser Phe Val Gly Cys Leu Lys 1505 1510 1515 1520 Asn Phe Gln Leu AspSer Lys Pro Leu Tyr Thr Pro Ser Ser Ser Phe 1525 1530 1535 Gly Val SerSer Cys Leu Gly Gly Pro Leu Glu Lys Gly Ile Tyr Phe 1540 1545 1550 SerGlu Glu Gly Gly His Val Val Leu Ala His Ser Val Leu Leu Gly 1555 15601565 Pro Glu Phe Lys Leu Val Phe Ser Ile Arg Pro Arg Ser Leu Thr Gly1570 1575 1580 Ile Leu Ile His Ile Gly Ser Gln Pro Gly Lys His Leu CysVal Tyr 1585 1590 1595 1600 Leu Glu Ala Gly Lys Val Thr Ala Ser Met AspSer Gly Ala Gly Gly 1605 1610 1615 Thr Ser Thr Ser Val Thr Pro Lys GlnSer Leu Cys Asp Gly Gln Trp 1620 1625 1630 His Ser Val Ala Val Thr IleLys Gln His Ile Leu His Leu Glu Leu 1635 1640 1645 Asp Thr Asp Ser SerTyr Thr Ala Gly Gln Ile Pro Phe Pro Pro Ala 1650 1655 1660 Ser Thr GlnGlu Pro Leu His Leu Gly Gly Ala Pro Ala Asn Leu Thr 1665 1670 1675 1680Thr Leu Arg Ile Pro Val Trp Lys Ser Phe Phe Gly Cys Leu Arg Asn 16851690 1695 Ile His Val Asn His Ile Pro Val Pro Val Thr Glu Ala Leu GluVal 1700 1705 1710 Gln Gly Pro Val Ser Leu Asn Gly Cys Pro Asp Gln 17151720 3 5170 DNA Homo sapiens CDS (1)..(5079) 3 cag caa agg gtg cca tttctt cag cct ccc ggt caa agt caa ctg caa 48 Gln Gln Arg Val Pro Phe LeuGln Pro Pro Gly Gln Ser Gln Leu Gln 1 5 10 15 gcg agt tat gtg gag tttaga ccc agc cag ggt tgt agc cct gga tac 96 Ala Ser Tyr Val Glu Phe ArgPro Ser Gln Gly Cys Ser Pro Gly Tyr 20 25 30 tat cgg gat cat aaa ggc ttgtat acc gga cgg tgt gtt ccc tgc aat 144 Tyr Arg Asp His Lys Gly Leu TyrThr Gly Arg Cys Val Pro Cys Asn 35 40 45 tgc aac gga cat tca aat caa tgccag gat ggc tca ggc ata tgt gtt 192 Cys Asn Gly His Ser Asn Gln Cys GlnAsp Gly Ser Gly Ile Cys Val 50 55 60 aac tgt cag cac aac acc gcg gga gagcac tgt gaa cgc tgc cag gag 240 Asn Cys Gln His Asn Thr Ala Gly Glu HisCys Glu Arg Cys Gln Glu 65 70 75 80 ggc tac tat ggc aac gcc gtc cac ggatcc tgc agg gcc tgc cca tgt 288 Gly Tyr Tyr Gly Asn Ala Val His Gly SerCys Arg Ala Cys Pro Cys 85 90 95 cct cac act aac agc ttt gcc act ggc tgtgtg gtg aat ggg gga gac 336 Pro His Thr Asn Ser Phe Ala Thr Gly Cys ValVal Asn Gly Gly Asp 100 105 110 gtg cgg tgc tcc tgc aaa gct ggg tac acagga aca cag tgt gaa agg 384 Val Arg Cys Ser Cys Lys Ala Gly Tyr Thr GlyThr Gln Cys Glu Arg 115 120 125 tgt gca ccg gga tat ttc ggg aat ccc cagaaa ttc gga ggt agc tgc 432 Cys Ala Pro Gly Tyr Phe Gly Asn Pro Gln LysPhe Gly Gly Ser Cys 130 135 140 caa cca tgc agt tgt aac agc aat ggc cagctg ggc agc tgt cat ccc 480 Gln Pro Cys Ser Cys Asn Ser Asn Gly Gln LeuGly Ser Cys His Pro 145 150 155 160 ctg act gga gac tgc ata aac caa gaaccc aaa gat agc agc cct gca 528 Leu Thr Gly Asp Cys Ile Asn Gln Glu ProLys Asp Ser Ser Pro Ala 165 170 175 gaa gaa tgt gat gat tgc gac agc tgtgtg atg acc ctc ctg aac gac 576 Glu Glu Cys Asp Asp Cys Asp Ser Cys ValMet Thr Leu Leu Asn Asp 180 185 190 ctg gcc acc atg ggc gag cag ctc cgcctg gtc aag tct cag ctg cag 624 Leu Ala Thr Met Gly Glu Gln Leu Arg LeuVal Lys Ser Gln Leu Gln 195 200 205 ggc ctg agt gcc agc gca ggg ctt ctggag cag atg agg cac atg gag 672 Gly Leu Ser Ala Ser Ala Gly Leu Leu GluGln Met Arg His Met Glu 210 215 220 acc cag gcc aag gac ctg agg aat cagttg ctc aac tac cgt tct gcc 720 Thr Gln Ala Lys Asp Leu Arg Asn Gln LeuLeu Asn Tyr Arg Ser Ala 225 230 235 240 att tca aat cat gga tca aaa atagaa ggc ctg gaa aga gaa ctg act 768 Ile Ser Asn His Gly Ser Lys Ile GluGly Leu Glu Arg Glu Leu Thr 245 250 255 gat ttg aat caa gaa ttt gag acttta caa gaa aag gct caa gta aat 816 Asp Leu Asn Gln Glu Phe Glu Thr LeuGln Glu Lys Ala Gln Val Asn 260 265 270 tcc aga aaa gca caa aca tta aacaac aat gtt aat cgg gca aca caa 864 Ser Arg Lys Ala Gln Thr Leu Asn AsnAsn Val Asn Arg Ala Thr Gln 275 280 285 agc gca aaa gaa cta gat gtg aagatt aaa aat gtc atc cgg aat gtg 912 Ser Ala Lys Glu Leu Asp Val Lys IleLys Asn Val Ile Arg Asn Val 290 295 300 cac att ctt tta aag cag atc tctggg aca gat gga gag gga aac aac 960 His Ile Leu Leu Lys Gln Ile Ser GlyThr Asp Gly Glu Gly Asn Asn 305 310 315 320 gtg cct tca ggt gac ttt tccaga gag tgg gct gaa gcc cag cgc atg 1008 Val Pro Ser Gly Asp Phe Ser ArgGlu Trp Ala Glu Ala Gln Arg Met 325 330 335 atg agg gaa ctg cgg aac aggaac ttt gga aag cac ctc aga gaa gca 1056 Met Arg Glu Leu Arg Asn Arg AsnPhe Gly Lys His Leu Arg Glu Ala 340 345 350 gaa gct gat aaa agg gag tcgcag ctc ttg ctg aac cgg ata agg acc 1104 Glu Ala Asp Lys Arg Glu Ser GlnLeu Leu Leu Asn Arg Ile Arg Thr 355 360 365 tgg cag aaa acc cac cag ggggag aac aat ggg ctt gct aac agt atc 1152 Trp Gln Lys Thr His Gln Gly GluAsn Asn Gly Leu Ala Asn Ser Ile 370 375 380 cgg gat tct tta aat gaa tacgaa gcc aaa ctc agt gac ctt cgt gct 1200 Arg Asp Ser Leu Asn Glu Tyr GluAla Lys Leu Ser Asp Leu Arg Ala 385 390 395 400 cgg ctg cag gag gca gctgcc caa gcc aag cag gca aat ggc ttg aac 1248 Arg Leu Gln Glu Ala Ala AlaGln Ala Lys Gln Ala Asn Gly Leu Asn 405 410 415 caa gaa aac gag aga gctttg gga gcc att cag aga caa gtg aaa gaa 1296 Gln Glu Asn Glu Arg Ala LeuGly Ala Ile Gln Arg Gln Val Lys Glu 420 425 430 ata aat tcc ctg cag agtgat ttc acc aag tat cta acc act gca gac 1344 Ile Asn Ser Leu Gln Ser AspPhe Thr Lys Tyr Leu Thr Thr Ala Asp 435 440 445 tca tct ttg ttg caa accaac att gcg ctg cag ctg atg gag aaa agc 1392 Ser Ser Leu Leu Gln Thr AsnIle Ala Leu Gln Leu Met Glu Lys Ser 450 455 460 cag aag gaa tat gaa aaatta gct gcc agt tta aat gaa gca aga caa 1440 Gln Lys Glu Tyr Glu Lys LeuAla Ala Ser Leu Asn Glu Ala Arg Gln 465 470 475 480 gaa cta agt gac aaagta aga gaa ctt tcc aga tct gct ggc aaa aca 1488 Glu Leu Ser Asp Lys ValArg Glu Leu Ser Arg Ser Ala Gly Lys Thr 485 490 495 tcc ctt gtg gag gaggca gaa aag cac gcg cgg tcc tta caa gag ctg 1536 Ser Leu Val Glu Glu AlaGlu Lys His Ala Arg Ser Leu Gln Glu Leu 500 505 510 gca aag cag ctg gaagag atc aag aga aac gcc agc ggg gat gag ctg 1584 Ala Lys Gln Leu Glu GluIle Lys Arg Asn Ala Ser Gly Asp Glu Leu 515 520 525 gtg cgc tgt gct gtggat gcc gcc acc gcc tac gag aac atc ctc aat 1632 Val Arg Cys Ala Val AspAla Ala Thr Ala Tyr Glu Asn Ile Leu Asn 530 535 540 gcc atc aaa gcg gccgag gac gca gcc aac agg gct gcc agt gca tct 1680 Ala Ile Lys Ala Ala GluAsp Ala Ala Asn Arg Ala Ala Ser Ala Ser 545 550 555 560 gaa tct gcc ctccag aca gtg ata aag gaa gat ctg cca aga aaa gct 1728 Glu Ser Ala Leu GlnThr Val Ile Lys Glu Asp Leu Pro Arg Lys Ala 565 570 575 aaa acc ctg agttcc aac agt gat aaa ctg tta aat gaa gcc aag atg 1776 Lys Thr Leu Ser SerAsn Ser Asp Lys Leu Leu Asn Glu Ala Lys Met 580 585 590 aca caa aag aagcta aag caa gaa gtc agt cca gct ctc aac aac cta 1824 Thr Gln Lys Lys LeuLys Gln Glu Val Ser Pro Ala Leu Asn Asn Leu 595 600 605 cag caa acc ctgaat att gtg aca gtt cag aaa gaa gtg ata gac acc 1872 Gln Gln Thr Leu AsnIle Val Thr Val Gln Lys Glu Val Ile Asp Thr 610 615 620 aat ctc aca actctc cga gat ggt ctt cat ggg ata cag aga ggt gat 1920 Asn Leu Thr Thr LeuArg Asp Gly Leu His Gly Ile Gln Arg Gly Asp 625 630 635 640 att gat gctatg atc agt agt gca aag agc atg gtc aga aag gcc aac 1968 Ile Asp Ala MetIle Ser Ser Ala Lys Ser Met Val Arg Lys Ala Asn 645 650 655 gac atc acagat gag gtt ctg gat ggg ctc aac ccc atc cag aca gat 2016 Asp Ile Thr AspGlu Val Leu Asp Gly Leu Asn Pro Ile Gln Thr Asp 660 665 670 gtg gaa agaatt aag gac acc tat ggg agg aca cag aac gaa gac ttc 2064 Val Glu Arg IleLys Asp Thr Tyr Gly Arg Thr Gln Asn Glu Asp Phe 675 680 685 aaa aag gctctg act gat gca gat aac tcg gtg aat aag tta acc aac 2112 Lys Lys Ala LeuThr Asp Ala Asp Asn Ser Val Asn Lys Leu Thr Asn 690 695 700 aaa cta cctgat ctt tgg cgc aag att gaa agt atc aac caa cag ctg 2160 Lys Leu Pro AspLeu Trp Arg Lys Ile Glu Ser Ile Asn Gln Gln Leu 705 710 715 720 ttg cccttg gga aac atc tct gac aac atg gac aga ata cga gaa cta 2208 Leu Pro LeuGly Asn Ile Ser Asp Asn Met Asp Arg Ile Arg Glu Leu 725 730 735 att cagcag gcc aga gat gct gcc agt aag gtt gct gtc ccc atg agg 2256 Ile Gln GlnAla Arg Asp Ala Ala Ser Lys Val Ala Val Pro Met Arg 740 745 750 ttc aatggt aaa tct gga gtc gaa gtc cga ctg cca aat gac ctg gaa 2304 Phe Asn GlyLys Ser Gly Val Glu Val Arg Leu Pro Asn Asp Leu Glu 755 760 765 gat ttgaaa gga tat aca tct ctg tcc ttg ttt ctc caa agg ccc aac 2352 Asp Leu LysGly Tyr Thr Ser Leu Ser Leu Phe Leu Gln Arg Pro Asn 770 775 780 tca agagaa aat ggg ggt act gag aat atg ttt gtg atg tac ctt gga 2400 Ser Arg GluAsn Gly Gly Thr Glu Asn Met Phe Val Met Tyr Leu Gly 785 790 795 800 aataaa gat gcc tcc cgg gac tac atc ggc atg gca gtt gtg gat ggc 2448 Asn LysAsp Ala Ser Arg Asp Tyr Ile Gly Met Ala Val Val Asp Gly 805 810 815 cagctc acc tgt gtc tac aac ctg ggg gac cgt gag gct gaa ctc caa 2496 Gln LeuThr Cys Val Tyr Asn Leu Gly Asp Arg Glu Ala Glu Leu Gln 820 825 830 gtggac cag atc ttg acc aag agt gag act aag gag gca gtt atg gat 2544 Val AspGln Ile Leu Thr Lys Ser Glu Thr Lys Glu Ala Val Met Asp 835 840 845 cgggtg aaa ttt cag aga att tat cag ttt gca agg ctt aat tac acc 2592 Arg ValLys Phe Gln Arg Ile Tyr Gln Phe Ala Arg Leu Asn Tyr Thr 850 855 860 aaagga gcc aca tcc agt aaa cca gaa aca ccc gga gtc tat gac atg 2640 Lys GlyAla Thr Ser Ser Lys Pro Glu Thr Pro Gly Val Tyr Asp Met 865 870 875 880gat ggt aga aat agc aat aca ctc ctt aat ttg gat cct gaa aat gtt 2688 AspGly Arg Asn Ser Asn Thr Leu Leu Asn Leu Asp Pro Glu Asn Val 885 890 895gta ttt tat gtt gga ggt tac cca cct gat ttt aaa ctt ccc agt cga 2736 ValPhe Tyr Val Gly Gly Tyr Pro Pro Asp Phe Lys Leu Pro Ser Arg 900 905 910cta agt ttc cct cca tac aaa ggt tgt att gaa tta gat gac ctc aat 2784 LeuSer Phe Pro Pro Tyr Lys Gly Cys Ile Glu Leu Asp Asp Leu Asn 915 920 925gaa aat gtt ctg agc ttg tac aac ttc aaa aaa aca ttc aat ctc aac 2832 GluAsn Val Leu Ser Leu Tyr Asn Phe Lys Lys Thr Phe Asn Leu Asn 930 935 940aca act gaa gtg gag cct tgt aga agg agg aag gaa gag tca gac aaa 2880 ThrThr Glu Val Glu Pro Cys Arg Arg Arg Lys Glu Glu Ser Asp Lys 945 950 955960 aat tat ttt gaa ggt acg ggc tat gct cga gtt cca act caa cca cat 2928Asn Tyr Phe Glu Gly Thr Gly Tyr Ala Arg Val Pro Thr Gln Pro His 965 970975 gct ccc atc cca acc ttt gga cag aca att cag acc acc gtg gat aga 2976Ala Pro Ile Pro Thr Phe Gly Gln Thr Ile Gln Thr Thr Val Asp Arg 980 985990 ggc ttg ctg ttc ttt gca gaa aac ggg gat cgc ttc ata tct cta aat 3024Gly Leu Leu Phe Phe Ala Glu Asn Gly Asp Arg Phe Ile Ser Leu Asn 995 10001005 ata gaa gat ggc aag ctc atg gtg aga tac aaa ctg aat tca gag cta3072 Ile Glu Asp Gly Lys Leu Met Val Arg Tyr Lys Leu Asn Ser Glu Leu1010 1015 1020 cca aaa gag aga gga gtt gga gac gcc ata aac aac ggc agagac cat 3120 Pro Lys Glu Arg Gly Val Gly Asp Ala Ile Asn Asn Gly Arg AspHis 1025 1030 1035 1040 tcg att cag atc aaa att gga aaa ctc caa aag cgtatg tgg ata aat 3168 Ser Ile Gln Ile Lys Ile Gly Lys Leu Gln Lys Arg MetTrp Ile Asn 1045 1050 1055 gtg gac gtt caa aac act ata att gat ggt gaagta ttt gat ttc agc 3216 Val Asp Val Gln Asn Thr Ile Ile Asp Gly Glu ValPhe Asp Phe Ser 1060 1065 1070 aca tat tat ctg gga gga att cca att gcaatc agg gaa aga ttt aac 3264 Thr Tyr Tyr Leu Gly Gly Ile Pro Ile Ala IleArg Glu Arg Phe Asn 1075 1080 1085 att tct acg cct gct ttc cga ggc tgcatg aaa aat ttg aag aaa acc 3312 Ile Ser Thr Pro Ala Phe Arg Gly Cys MetLys Asn Leu Lys Lys Thr 1090 1095 1100 agt ggt gtc gtt aga ttg aat gatact gtg gga gta acc aaa aag tgc 3360 Ser Gly Val Val Arg Leu Asn Asp ThrVal Gly Val Thr Lys Lys Cys 1105 1110 1115 1120 tcg gaa gac tgg aag cttgtg cga tct gcc tca ttc tcc aga gga gga 3408 Ser Glu Asp Trp Lys Leu ValArg Ser Ala Ser Phe Ser Arg Gly Gly 1125 1130 1135 caa ttg agt ttc actgat ttg ggc tta cca cct act gac cac ctc cag 3456 Gln Leu Ser Phe Thr AspLeu Gly Leu Pro Pro Thr Asp His Leu Gln 1140 1145 1150 gcc tca ttt ggattt cag acc ttt caa ccc agt ggc ata tta tta gat 3504 Ala Ser Phe Gly PheGln Thr Phe Gln Pro Ser Gly Ile Leu Leu Asp 1155 1160 1165 cat cag acatgg aca agg aac ctg cag gtc act ctg gaa gat ggt tac 3552 His Gln Thr TrpThr Arg Asn Leu Gln Val Thr Leu Glu Asp Gly Tyr 1170 1175 1180 att gaattg agc acc agc gat agc ggc ggc cca att ttt aaa tct cca 3600 Ile Glu LeuSer Thr Ser Asp Ser Gly Gly Pro Ile Phe Lys Ser Pro 1185 1190 1195 1200cag acg tat atg gat ggt tta ctg cat tat gta tct gta ata agc gac 3648 GlnThr Tyr Met Asp Gly Leu Leu His Tyr Val Ser Val Ile Ser Asp 1205 12101215 aac tct gga cta cgg ctt ctc atc gat gac cag ctt ctg aga aat agc3696 Asn Ser Gly Leu Arg Leu Leu Ile Asp Asp Gln Leu Leu Arg Asn Ser1220 1225 1230 aaa agg cta aaa cac att tca agt tcc cgg cag tct ctg cgtctg ggc 3744 Lys Arg Leu Lys His Ile Ser Ser Ser Arg Gln Ser Leu Arg LeuGly 1235 1240 1245 ggg agc aat ttt gag ggt tgt att agc aat gtt ttt gtccag agg tta 3792 Gly Ser Asn Phe Glu Gly Cys Ile Ser Asn Val Phe Val GlnArg Leu 1250 1255 1260 tca ctg agt cct gaa gtc cta gat ttg acc agt aactct ctc aag aga 3840 Ser Leu Ser Pro Glu Val Leu Asp Leu Thr Ser Asn SerLeu Lys Arg 1265 1270 1275 1280 gat gtg tcc ctg gga ggc tgc agt tta aacaaa cca cct ttt cta atg 3888 Asp Val Ser Leu Gly Gly Cys Ser Leu Asn LysPro Pro Phe Leu Met 1285 1290 1295 ttg ctt aaa ggt tct acc agg ttt aacaag acc aag act ttt cgt atc 3936 Leu Leu Lys Gly Ser Thr Arg Phe Asn LysThr Lys Thr Phe Arg Ile 1300 1305 1310 aac cag ctg ttg cag gac aca ccagtg gcc tcc cca agg agc gtg aag 3984 Asn Gln Leu Leu Gln Asp Thr Pro ValAla Ser Pro Arg Ser Val Lys 1315 1320 1325 gtg tgg caa gat gct tgc tcacca ctt ccc aag acc cag gcc aat cat 4032 Val Trp Gln Asp Ala Cys Ser ProLeu Pro Lys Thr Gln Ala Asn His 1330 1335 1340 gga gcc ctc cag ttt ggggac att ccc acc agc cac ttg cta ttc aag 4080 Gly Ala Leu Gln Phe Gly AspIle Pro Thr Ser His Leu Leu Phe Lys 1345 1350 1355 1360 ctt cct cag gagctg ctg aaa ccc agg tca cag ttt gct gtg gac atg 4128 Leu Pro Gln Glu LeuLeu Lys Pro Arg Ser Gln Phe Ala Val Asp Met 1365 1370 1375 cag aca acatcc tcc aga gga ctg gtg ttt cac acg ggc act aag aac 4176 Gln Thr Thr SerSer Arg Gly Leu Val Phe His Thr Gly Thr Lys Asn 1380 1385 1390 tcc tttatg gct ctt tat ctt tca aaa gga cgt ctg gtc ttt gca ctg 4224 Ser Phe MetAla Leu Tyr Leu Ser Lys Gly Arg Leu Val Phe Ala Leu 1395 1400 1405 gggaca gat ggg aaa aaa ttg agg atc aaa agc aag gag aaa tgc aat 4272 Gly ThrAsp Gly Lys Lys Leu Arg Ile Lys Ser Lys Glu Lys Cys Asn 1410 1415 1420gat ggg aaa tgg cac acg gtg gtg ttt ggc cat gat ggg gaa aag ggg 4320 AspGly Lys Trp His Thr Val Val Phe Gly His Asp Gly Glu Lys Gly 1425 14301435 1440 cgc ttg gtt gtg gat gga ctg agg gcc cgg gag gga agt ttg cctgga 4368 Arg Leu Val Val Asp Gly Leu Arg Ala Arg Glu Gly Ser Leu Pro Gly1445 1450 1455 aac tcc acc atc agc atc aga gcg cca gtt tac ctg gga tcacct cca 4416 Asn Ser Thr Ile Ser Ile Arg Ala Pro Val Tyr Leu Gly Ser ProPro 1460 1465 1470 tca ggg aaa cca aag agc ctc ccc aca aac agc ttt gtggga tgc ctg 4464 Ser Gly Lys Pro Lys Ser Leu Pro Thr Asn Ser Phe Val GlyCys Leu 1475 1480 1485 aag aac ttt cag ctg gat tca aaa ccc ttg tat acccct tct tca agc 4512 Lys Asn Phe Gln Leu Asp Ser Lys Pro Leu Tyr Thr ProSer Ser Ser 1490 1495 1500 ttc ggg gtg tct tcc tgc ttg ggt ggt cct ttggag aaa ggc att tat 4560 Phe Gly Val Ser Ser Cys Leu Gly Gly Pro Leu GluLys Gly Ile Tyr 1505 1510 1515 1520 ttc tct gaa gaa gga ggt cat gtc gtcttg gct cac tct gta ttg ttg 4608 Phe Ser Glu Glu Gly Gly His Val Val LeuAla His Ser Val Leu Leu 1525 1530 1535 ggg cca gaa ttt aag ctt gtt ttcagc atc cgc cca aga agt ctc act 4656 Gly Pro Glu Phe Lys Leu Val Phe SerIle Arg Pro Arg Ser Leu Thr 1540 1545 1550 ggg atc cta ata cac atc ggaagt cag ccc ggg aag cac tta tgt gtt 4704 Gly Ile Leu Ile His Ile Gly SerGln Pro Gly Lys His Leu Cys Val 1555 1560 1565 tac ctg gag gca gga aaggtc acg gcc tct atg gac agt ggg gca ggt 4752 Tyr Leu Glu Ala Gly Lys ValThr Ala Ser Met Asp Ser Gly Ala Gly 1570 1575 1580 ggg acc tca acg tcggtc aca cca aag cag tct ctg tgt gat gga cag 4800 Gly Thr Ser Thr Ser ValThr Pro Lys Gln Ser Leu Cys Asp Gly Gln 1585 1590 1595 1600 tgg cac tcggtg gca gtc acc ata aaa caa cac atc ctg cac ctg gaa 4848 Trp His Ser ValAla Val Thr Ile Lys Gln His Ile Leu His Leu Glu 1605 1610 1615 ctg gacaca gac agt agc tac aca gct gga cag atc ccc ttc cca cct 4896 Leu Asp ThrAsp Ser Ser Tyr Thr Ala Gly Gln Ile Pro Phe Pro Pro 1620 1625 1630 gccagc act caa gag cca cta cac ctt gga ggt gct cca gcc aat ttg 4944 Ala SerThr Gln Glu Pro Leu His Leu Gly Gly Ala Pro Ala Asn Leu 1635 1640 1645acg aca ctg agg atc cct gtg tgg aaa tca ttc ttt ggc tgt ctg agg 4992 ThrThr Leu Arg Ile Pro Val Trp Lys Ser Phe Phe Gly Cys Leu Arg 1650 16551660 aat att cat gtc aat cac atc cct gtc cct gtc act gaa gcc ttg gaa5040 Asn Ile His Val Asn His Ile Pro Val Pro Val Thr Glu Ala Leu Glu1665 1670 1675 1680 gtc cag ggg cct gtc agt ctg aat ggt tgt cct gac cagtaacccaagc 5089 Val Gln Gly Pro Val Ser Leu Asn Gly Cys Pro Asp Gln 16851690 ctatttcaca gcaaggaaat tcaccttcaa aagcactgat tacccaatgc acctccctcc5149 ccagctcgag atcattcttc a 5170 4 1693 PRT Homo sapiens 4 Gln Gln ArgVal Pro Phe Leu Gln Pro Pro Gly Gln Ser Gln Leu Gln 1 5 10 15 Ala SerTyr Val Glu Phe Arg Pro Ser Gln Gly Cys Ser Pro Gly Tyr 20 25 30 Tyr ArgAsp His Lys Gly Leu Tyr Thr Gly Arg Cys Val Pro Cys Asn 35 40 45 Cys AsnGly His Ser Asn Gln Cys Gln Asp Gly Ser Gly Ile Cys Val 50 55 60 Asn CysGln His Asn Thr Ala Gly Glu His Cys Glu Arg Cys Gln Glu 65 70 75 80 GlyTyr Tyr Gly Asn Ala Val His Gly Ser Cys Arg Ala Cys Pro Cys 85 90 95 ProHis Thr Asn Ser Phe Ala Thr Gly Cys Val Val Asn Gly Gly Asp 100 105 110Val Arg Cys Ser Cys Lys Ala Gly Tyr Thr Gly Thr Gln Cys Glu Arg 115 120125 Cys Ala Pro Gly Tyr Phe Gly Asn Pro Gln Lys Phe Gly Gly Ser Cys 130135 140 Gln Pro Cys Ser Cys Asn Ser Asn Gly Gln Leu Gly Ser Cys His Pro145 150 155 160 Leu Thr Gly Asp Cys Ile Asn Gln Glu Pro Lys Asp Ser SerPro Ala 165 170 175 Glu Glu Cys Asp Asp Cys Asp Ser Cys Val Met Thr LeuLeu Asn Asp 180 185 190 Leu Ala Thr Met Gly Glu Gln Leu Arg Leu Val LysSer Gln Leu Gln 195 200 205 Gly Leu Ser Ala Ser Ala Gly Leu Leu Glu GlnMet Arg His Met Glu 210 215 220 Thr Gln Ala Lys Asp Leu Arg Asn Gln LeuLeu Asn Tyr Arg Ser Ala 225 230 235 240 Ile Ser Asn His Gly Ser Lys IleGlu Gly Leu Glu Arg Glu Leu Thr 245 250 255 Asp Leu Asn Gln Glu Phe GluThr Leu Gln Glu Lys Ala Gln Val Asn 260 265 270 Ser Arg Lys Ala Gln ThrLeu Asn Asn Asn Val Asn Arg Ala Thr Gln 275 280 285 Ser Ala Lys Glu LeuAsp Val Lys Ile Lys Asn Val Ile Arg Asn Val 290 295 300 His Ile Leu LeuLys Gln Ile Ser Gly Thr Asp Gly Glu Gly Asn Asn 305 310 315 320 Val ProSer Gly Asp Phe Ser Arg Glu Trp Ala Glu Ala Gln Arg Met 325 330 335 MetArg Glu Leu Arg Asn Arg Asn Phe Gly Lys His Leu Arg Glu Ala 340 345 350Glu Ala Asp Lys Arg Glu Ser Gln Leu Leu Leu Asn Arg Ile Arg Thr 355 360365 Trp Gln Lys Thr His Gln Gly Glu Asn Asn Gly Leu Ala Asn Ser Ile 370375 380 Arg Asp Ser Leu Asn Glu Tyr Glu Ala Lys Leu Ser Asp Leu Arg Ala385 390 395 400 Arg Leu Gln Glu Ala Ala Ala Gln Ala Lys Gln Ala Asn GlyLeu Asn 405 410 415 Gln Glu Asn Glu Arg Ala Leu Gly Ala Ile Gln Arg GlnVal Lys Glu 420 425 430 Ile Asn Ser Leu Gln Ser Asp Phe Thr Lys Tyr LeuThr Thr Ala Asp 435 440 445 Ser Ser Leu Leu Gln Thr Asn Ile Ala Leu GlnLeu Met Glu Lys Ser 450 455 460 Gln Lys Glu Tyr Glu Lys Leu Ala Ala SerLeu Asn Glu Ala Arg Gln 465 470 475 480 Glu Leu Ser Asp Lys Val Arg GluLeu Ser Arg Ser Ala Gly Lys Thr 485 490 495 Ser Leu Val Glu Glu Ala GluLys His Ala Arg Ser Leu Gln Glu Leu 500 505 510 Ala Lys Gln Leu Glu GluIle Lys Arg Asn Ala Ser Gly Asp Glu Leu 515 520 525 Val Arg Cys Ala ValAsp Ala Ala Thr Ala Tyr Glu Asn Ile Leu Asn 530 535 540 Ala Ile Lys AlaAla Glu Asp Ala Ala Asn Arg Ala Ala Ser Ala Ser 545 550 555 560 Glu SerAla Leu Gln Thr Val Ile Lys Glu Asp Leu Pro Arg Lys Ala 565 570 575 LysThr Leu Ser Ser Asn Ser Asp Lys Leu Leu Asn Glu Ala Lys Met 580 585 590Thr Gln Lys Lys Leu Lys Gln Glu Val Ser Pro Ala Leu Asn Asn Leu 595 600605 Gln Gln Thr Leu Asn Ile Val Thr Val Gln Lys Glu Val Ile Asp Thr 610615 620 Asn Leu Thr Thr Leu Arg Asp Gly Leu His Gly Ile Gln Arg Gly Asp625 630 635 640 Ile Asp Ala Met Ile Ser Ser Ala Lys Ser Met Val Arg LysAla Asn 645 650 655 Asp Ile Thr Asp Glu Val Leu Asp Gly Leu Asn Pro IleGln Thr Asp 660 665 670 Val Glu Arg Ile Lys Asp Thr Tyr Gly Arg Thr GlnAsn Glu Asp Phe 675 680 685 Lys Lys Ala Leu Thr Asp Ala Asp Asn Ser ValAsn Lys Leu Thr Asn 690 695 700 Lys Leu Pro Asp Leu Trp Arg Lys Ile GluSer Ile Asn Gln Gln Leu 705 710 715 720 Leu Pro Leu Gly Asn Ile Ser AspAsn Met Asp Arg Ile Arg Glu Leu 725 730 735 Ile Gln Gln Ala Arg Asp AlaAla Ser Lys Val Ala Val Pro Met Arg 740 745 750 Phe Asn Gly Lys Ser GlyVal Glu Val Arg Leu Pro Asn Asp Leu Glu 755 760 765 Asp Leu Lys Gly TyrThr Ser Leu Ser Leu Phe Leu Gln Arg Pro Asn 770 775 780 Ser Arg Glu AsnGly Gly Thr Glu Asn Met Phe Val Met Tyr Leu Gly 785 790 795 800 Asn LysAsp Ala Ser Arg Asp Tyr Ile Gly Met Ala Val Val Asp Gly 805 810 815 GlnLeu Thr Cys Val Tyr Asn Leu Gly Asp Arg Glu Ala Glu Leu Gln 820 825 830Val Asp Gln Ile Leu Thr Lys Ser Glu Thr Lys Glu Ala Val Met Asp 835 840845 Arg Val Lys Phe Gln Arg Ile Tyr Gln Phe Ala Arg Leu Asn Tyr Thr 850855 860 Lys Gly Ala Thr Ser Ser Lys Pro Glu Thr Pro Gly Val Tyr Asp Met865 870 875 880 Asp Gly Arg Asn Ser Asn Thr Leu Leu Asn Leu Asp Pro GluAsn Val 885 890 895 Val Phe Tyr Val Gly Gly Tyr Pro Pro Asp Phe Lys LeuPro Ser Arg 900 905 910 Leu Ser Phe Pro Pro Tyr Lys Gly Cys Ile Glu LeuAsp Asp Leu Asn 915 920 925 Glu Asn Val Leu Ser Leu Tyr Asn Phe Lys LysThr Phe Asn Leu Asn 930 935 940 Thr Thr Glu Val Glu Pro Cys Arg Arg ArgLys Glu Glu Ser Asp Lys 945 950 955 960 Asn Tyr Phe Glu Gly Thr Gly TyrAla Arg Val Pro Thr Gln Pro His 965 970 975 Ala Pro Ile Pro Thr Phe GlyGln Thr Ile Gln Thr Thr Val Asp Arg 980 985 990 Gly Leu Leu Phe Phe AlaGlu Asn Gly Asp Arg Phe Ile Ser Leu Asn 995 1000 1005 Ile Glu Asp GlyLys Leu Met Val Arg Tyr Lys Leu Asn Ser Glu Leu 1010 1015 1020 Pro LysGlu Arg Gly Val Gly Asp Ala Ile Asn Asn Gly Arg Asp His 1025 1030 10351040 Ser Ile Gln Ile Lys Ile Gly Lys Leu Gln Lys Arg Met Trp Ile Asn1045 1050 1055 Val Asp Val Gln Asn Thr Ile Ile Asp Gly Glu Val Phe AspPhe Ser 1060 1065 1070 Thr Tyr Tyr Leu Gly Gly Ile Pro Ile Ala Ile ArgGlu Arg Phe Asn 1075 1080 1085 Ile Ser Thr Pro Ala Phe Arg Gly Cys MetLys Asn Leu Lys Lys Thr 1090 1095 1100 Ser Gly Val Val Arg Leu Asn AspThr Val Gly Val Thr Lys Lys Cys 1105 1110 1115 1120 Ser Glu Asp Trp LysLeu Val Arg Ser Ala Ser Phe Ser Arg Gly Gly 1125 1130 1135 Gln Leu SerPhe Thr Asp Leu Gly Leu Pro Pro Thr Asp His Leu Gln 1140 1145 1150 AlaSer Phe Gly Phe Gln Thr Phe Gln Pro Ser Gly Ile Leu Leu Asp 1155 11601165 His Gln Thr Trp Thr Arg Asn Leu Gln Val Thr Leu Glu Asp Gly Tyr1170 1175 1180 Ile Glu Leu Ser Thr Ser Asp Ser Gly Gly Pro Ile Phe LysSer Pro 1185 1190 1195 1200 Gln Thr Tyr Met Asp Gly Leu Leu His Tyr ValSer Val Ile Ser Asp 1205 1210 1215 Asn Ser Gly Leu Arg Leu Leu Ile AspAsp Gln Leu Leu Arg Asn Ser 1220 1225 1230 Lys Arg Leu Lys His Ile SerSer Ser Arg Gln Ser Leu Arg Leu Gly 1235 1240 1245 Gly Ser Asn Phe GluGly Cys Ile Ser Asn Val Phe Val Gln Arg Leu 1250 1255 1260 Ser Leu SerPro Glu Val Leu Asp Leu Thr Ser Asn Ser Leu Lys Arg 1265 1270 1275 1280Asp Val Ser Leu Gly Gly Cys Ser Leu Asn Lys Pro Pro Phe Leu Met 12851290 1295 Leu Leu Lys Gly Ser Thr Arg Phe Asn Lys Thr Lys Thr Phe ArgIle 1300 1305 1310 Asn Gln Leu Leu Gln Asp Thr Pro Val Ala Ser Pro ArgSer Val Lys 1315 1320 1325 Val Trp Gln Asp Ala Cys Ser Pro Leu Pro LysThr Gln Ala Asn His 1330 1335 1340 Gly Ala Leu Gln Phe Gly Asp Ile ProThr Ser His Leu Leu Phe Lys 1345 1350 1355 1360 Leu Pro Gln Glu Leu LeuLys Pro Arg Ser Gln Phe Ala Val Asp Met 1365 1370 1375 Gln Thr Thr SerSer Arg Gly Leu Val Phe His Thr Gly Thr Lys Asn 1380 1385 1390 Ser PheMet Ala Leu Tyr Leu Ser Lys Gly Arg Leu Val Phe Ala Leu 1395 1400 1405Gly Thr Asp Gly Lys Lys Leu Arg Ile Lys Ser Lys Glu Lys Cys Asn 14101415 1420 Asp Gly Lys Trp His Thr Val Val Phe Gly His Asp Gly Glu LysGly 1425 1430 1435 1440 Arg Leu Val Val Asp Gly Leu Arg Ala Arg Glu GlySer Leu Pro Gly 1445 1450 1455 Asn Ser Thr Ile Ser Ile Arg Ala Pro ValTyr Leu Gly Ser Pro Pro 1460 1465 1470 Ser Gly Lys Pro Lys Ser Leu ProThr Asn Ser Phe Val Gly Cys Leu 1475 1480 1485 Lys Asn Phe Gln Leu AspSer Lys Pro Leu Tyr Thr Pro Ser Ser Ser 1490 1495 1500 Phe Gly Val SerSer Cys Leu Gly Gly Pro Leu Glu Lys Gly Ile Tyr 1505 1510 1515 1520 PheSer Glu Glu Gly Gly His Val Val Leu Ala His Ser Val Leu Leu 1525 15301535 Gly Pro Glu Phe Lys Leu Val Phe Ser Ile Arg Pro Arg Ser Leu Thr1540 1545 1550 Gly Ile Leu Ile His Ile Gly Ser Gln Pro Gly Lys His LeuCys Val 1555 1560 1565 Tyr Leu Glu Ala Gly Lys Val Thr Ala Ser Met AspSer Gly Ala Gly 1570 1575 1580 Gly Thr Ser Thr Ser Val Thr Pro Lys GlnSer Leu Cys Asp Gly Gln 1585 1590 1595 1600 Trp His Ser Val Ala Val ThrIle Lys Gln His Ile Leu His Leu Glu 1605 1610 1615 Leu Asp Thr Asp SerSer Tyr Thr Ala Gly Gln Ile Pro Phe Pro Pro 1620 1625 1630 Ala Ser ThrGln Glu Pro Leu His Leu Gly Gly Ala Pro Ala Asn Leu 1635 1640 1645 ThrThr Leu Arg Ile Pro Val Trp Lys Ser Phe Phe Gly Cys Leu Arg 1650 16551660 Asn Ile His Val Asn His Ile Pro Val Pro Val Thr Glu Ala Leu Glu1665 1670 1675 1680 Val Gln Gly Pro Val Ser Leu Asn Gly Cys Pro Asp Gln1685 1690 5 5433 DNA Homo sapiens CDS (1)..(5139) sig_peptide (1)..(60)5 atg gga tgg ctg tgg atc ttt ggg gca gcc ctg ggg cag tgt ctg ggc 48 MetGly Trp Leu Trp Ile Phe Gly Ala Ala Leu Gly Gln Cys Leu Gly 1 5 10 15tac agt tca cag cag caa agg gtg cca ttt ctt cag cct ccc ggt caa 96 TyrSer Ser Gln Gln Gln Arg Val Pro Phe Leu Gln Pro Pro Gly Gln 20 25 30 agtcaa ctg caa gcg agt tat gtg gag ttt aga ccc agc cag ggt tgt 144 Ser GlnLeu Gln Ala Ser Tyr Val Glu Phe Arg Pro Ser Gln Gly Cys 35 40 45 agc cctgga tac tat cgg gat cat aaa ggc ttg tat acc gga cgg tgt 192 Ser Pro GlyTyr Tyr Arg Asp His Lys Gly Leu Tyr Thr Gly Arg Cys 50 55 60 gtt ccc tgcaat tgc aac gga cat tca aat caa tgc cag gat ggc tca 240 Val Pro Cys AsnCys Asn Gly His Ser Asn Gln Cys Gln Asp Gly Ser 65 70 75 80 ggc ata tgtgtt aac tgt cag cac aac acc gcg gga gag cac tgt gaa 288 Gly Ile Cys ValAsn Cys Gln His Asn Thr Ala Gly Glu His Cys Glu 85 90 95 cgc tgc cag gagggc tac tat ggc aac gcc gtc cac gga tcc tgc agg 336 Arg Cys Gln Glu GlyTyr Tyr Gly Asn Ala Val His Gly Ser Cys Arg 100 105 110 gcc tgc cca tgtcct cac act aac agc ttt gcc act ggc tgt gtg gtg 384 Ala Cys Pro Cys ProHis Thr Asn Ser Phe Ala Thr Gly Cys Val Val 115 120 125 aat ggg gga gacgtg cgg tgc tcc tgc aaa gct ggg tac aca gga aca 432 Asn Gly Gly Asp ValArg Cys Ser Cys Lys Ala Gly Tyr Thr Gly Thr 130 135 140 cag tgt gaa aggtgt gca ccg gga tat ttc ggg aat ccc cag aaa ttc 480 Gln Cys Glu Arg CysAla Pro Gly Tyr Phe Gly Asn Pro Gln Lys Phe 145 150 155 160 gga ggt agctgc caa cca tgc agt tgt aac agc aat ggc cag ctg ggc 528 Gly Gly Ser CysGln Pro Cys Ser Cys Asn Ser Asn Gly Gln Leu Gly 165 170 175 agc tgt catccc ctg act gga gac tgc ata aac caa gaa ccc aaa gat 576 Ser Cys His ProLeu Thr Gly Asp Cys Ile Asn Gln Glu Pro Lys Asp 180 185 190 agc agc cctgca gaa gaa tgt gat gat tgc gac agc tgt gtg atg acc 624 Ser Ser Pro AlaGlu Glu Cys Asp Asp Cys Asp Ser Cys Val Met Thr 195 200 205 ctc ctg aacgac ctg gcc acc atg ggc gag cag ctc cgc ctg gtc aag 672 Leu Leu Asn AspLeu Ala Thr Met Gly Glu Gln Leu Arg Leu Val Lys 210 215 220 tct cag ctgcag ggc ctg agt gcc agc gca ggg ctt ctg gag cag atg 720 Ser Gln Leu GlnGly Leu Ser Ala Ser Ala Gly Leu Leu Glu Gln Met 225 230 235 240 agg cacatg gag acc cag gcc aag gac ctg agg aat cag ttg ctc aac 768 Arg His MetGlu Thr Gln Ala Lys Asp Leu Arg Asn Gln Leu Leu Asn 245 250 255 tac cgttct gcc att tca aat cat gga tca aaa ata gaa ggc ctg gaa 816 Tyr Arg SerAla Ile Ser Asn His Gly Ser Lys Ile Glu Gly Leu Glu 260 265 270 aga gaactg act gat ttg aat caa gaa ttt gag act ttg caa gaa aag 864 Arg Glu LeuThr Asp Leu Asn Gln Glu Phe Glu Thr Leu Gln Glu Lys 275 280 285 gct caagta aat tcc aga aaa gca caa aca tta aac aac aat gtt aat 912 Ala Gln ValAsn Ser Arg Lys Ala Gln Thr Leu Asn Asn Asn Val Asn 290 295 300 cgg gcaaca caa agc gca aaa gaa ctg gat gtg aag att aaa aat gtc 960 Arg Ala ThrGln Ser Ala Lys Glu Leu Asp Val Lys Ile Lys Asn Val 305 310 315 320 atccgg aat gtg cac att ctt tta aag cag atc tct ggg aca gat gga 1008 Ile ArgAsn Val His Ile Leu Leu Lys Gln Ile Ser Gly Thr Asp Gly 325 330 335 gaggga aac aac gtg cct tca ggt gac ttt tcc aga gag tgg gct gaa 1056 Glu GlyAsn Asn Val Pro Ser Gly Asp Phe Ser Arg Glu Trp Ala Glu 340 345 350 gcccag cgc atg atg agg gaa ctg cgg aac agg aac ttt gga aag cac 1104 Ala GlnArg Met Met Arg Glu Leu Arg Asn Arg Asn Phe Gly Lys His 355 360 365 ctcaga gaa gca gaa gct gat aaa agg gag tcg cag ctc ttg ctg aac 1152 Leu ArgGlu Ala Glu Ala Asp Lys Arg Glu Ser Gln Leu Leu Leu Asn 370 375 380 cggata agg acc tgg cag aaa acc cac cag ggg gag aac aat ggg ctt 1200 Arg IleArg Thr Trp Gln Lys Thr His Gln Gly Glu Asn Asn Gly Leu 385 390 395 400gct aac agt atc cgg gat tct tta aat gaa tac gaa gcc aaa ctc agt 1248 AlaAsn Ser Ile Arg Asp Ser Leu Asn Glu Tyr Glu Ala Lys Leu Ser 405 410 415gac ctt cgt gct cgg ctg cag gag gca gct gcc caa gcc aag cag gca 1296 AspLeu Arg Ala Arg Leu Gln Glu Ala Ala Ala Gln Ala Lys Gln Ala 420 425 430aat ggc ttg aac caa gaa aac gag aga gct ttg gga gcc att cag aga 1344 AsnGly Leu Asn Gln Glu Asn Glu Arg Ala Leu Gly Ala Ile Gln Arg 435 440 445caa gtg aaa gaa ata aat tcc ctg cag agt gat ttc acc aag tat cta 1392 GlnVal Lys Glu Ile Asn Ser Leu Gln Ser Asp Phe Thr Lys Tyr Leu 450 455 460acc act gca gac tca tct ttg ttg caa acc aac att gcg ctg cag ctg 1440 ThrThr Ala Asp Ser Ser Leu Leu Gln Thr Asn Ile Ala Leu Gln Leu 465 470 475480 atg gag aaa agc cag aag gaa tat gaa aaa tta gct gcc agt tta aat 1488Met Glu Lys Ser Gln Lys Glu Tyr Glu Lys Leu Ala Ala Ser Leu Asn 485 490495 gaa gca aga caa gaa cta agt gac aaa gta aga gaa ctt tcc aga tct 1536Glu Ala Arg Gln Glu Leu Ser Asp Lys Val Arg Glu Leu Ser Arg Ser 500 505510 gct ggc aaa aca tcc ctt gtg gag gag gca gaa aag cac gcg cgg tcc 1584Ala Gly Lys Thr Ser Leu Val Glu Glu Ala Glu Lys His Ala Arg Ser 515 520525 tta caa gag ctg gca aag cag ctg gaa gag atc aag aga aac gcc agc 1632Leu Gln Glu Leu Ala Lys Gln Leu Glu Glu Ile Lys Arg Asn Ala Ser 530 535540 ggg gat gag ctg gtg cgc tgt gct gtg gat gcc gcc acc gcc tac gag 1680Gly Asp Glu Leu Val Arg Cys Ala Val Asp Ala Ala Thr Ala Tyr Glu 545 550555 560 aac atc ctc aat gcc atc aaa gcg gcc gag gac gca gcc aac agg gct1728 Asn Ile Leu Asn Ala Ile Lys Ala Ala Glu Asp Ala Ala Asn Arg Ala 565570 575 gcc agt gca tct gaa tct gcc ctc cag aca gtg ata aag gaa gat ctg1776 Ala Ser Ala Ser Glu Ser Ala Leu Gln Thr Val Ile Lys Glu Asp Leu 580585 590 cca aga aaa gct aaa acc ctg agt tcc aac agt gat aaa ctg tta aat1824 Pro Arg Lys Ala Lys Thr Leu Ser Ser Asn Ser Asp Lys Leu Leu Asn 595600 605 gaa gcc aag atg aca caa aag aag cta aag caa gaa gtc agt cca gct1872 Glu Ala Lys Met Thr Gln Lys Lys Leu Lys Gln Glu Val Ser Pro Ala 610615 620 ctc aac aac cta cag caa acc ctg aat att gtg aca gtt cag aaa gaa1920 Leu Asn Asn Leu Gln Gln Thr Leu Asn Ile Val Thr Val Gln Lys Glu 625630 635 640 gtg ata gac acc aat ctc aca act ctc cga gat ggt ctt cat gggata 1968 Val Ile Asp Thr Asn Leu Thr Thr Leu Arg Asp Gly Leu His Gly Ile645 650 655 cag aga ggt gat att gat gct atg atc agt agt gca aag agc atggtc 2016 Gln Arg Gly Asp Ile Asp Ala Met Ile Ser Ser Ala Lys Ser Met Val660 665 670 aga aag gcc aac gac atc aca gat gag gtt ctg gat ggg ctc aacccc 2064 Arg Lys Ala Asn Asp Ile Thr Asp Glu Val Leu Asp Gly Leu Asn Pro675 680 685 atc cag aca gat gtg gaa aga att aag gac acc tat ggg agg acacag 2112 Ile Gln Thr Asp Val Glu Arg Ile Lys Asp Thr Tyr Gly Arg Thr Gln690 695 700 aac gaa gac ttc aaa aag gct ctg act gat gca gat aac tcg gtgaat 2160 Asn Glu Asp Phe Lys Lys Ala Leu Thr Asp Ala Asp Asn Ser Val Asn705 710 715 720 aag tta acc aac aaa cta cct gat ctt tgg cgc aag att gaaagt atc 2208 Lys Leu Thr Asn Lys Leu Pro Asp Leu Trp Arg Lys Ile Glu SerIle 725 730 735 aac caa cag ctg ttg ccc ttg gga aac atc tct gac aac atggac aga 2256 Asn Gln Gln Leu Leu Pro Leu Gly Asn Ile Ser Asp Asn Met AspArg 740 745 750 ata cga gaa cta att cag cag gcc aga gat gct gcc agt aaggtt gct 2304 Ile Arg Glu Leu Ile Gln Gln Ala Arg Asp Ala Ala Ser Lys ValAla 755 760 765 gtc ccc atg agg ttc aat ggt aaa tct gga gtc gaa gtc cgactg cca 2352 Val Pro Met Arg Phe Asn Gly Lys Ser Gly Val Glu Val Arg LeuPro 770 775 780 aat gac ctg gaa gat ttg aaa gga tat aca tct ctg tcc ttgttt ctc 2400 Asn Asp Leu Glu Asp Leu Lys Gly Tyr Thr Ser Leu Ser Leu PheLeu 785 790 795 800 caa agg ccc aac tca aga gaa aat ggg ggt act gag aatatg ttt gtg 2448 Gln Arg Pro Asn Ser Arg Glu Asn Gly Gly Thr Glu Asn MetPhe Val 805 810 815 atg tac ctt gga aat aaa gat gcc tcc cgg gac tac atcggc atg gca 2496 Met Tyr Leu Gly Asn Lys Asp Ala Ser Arg Asp Tyr Ile GlyMet Ala 820 825 830 gtt gtg gat ggc cag ctc acc tgt gtc tac aac ctg ggggac cgt gag 2544 Val Val Asp Gly Gln Leu Thr Cys Val Tyr Asn Leu Gly AspArg Glu 835 840 845 gct gaa ctc caa gtg gac cag atc ttg acc aag agt gagact aag gag 2592 Ala Glu Leu Gln Val Asp Gln Ile Leu Thr Lys Ser Glu ThrLys Glu 850 855 860 gca gtt atg gat cgg gtg aaa ttt cag aga att tat cagttt gca agg 2640 Ala Val Met Asp Arg Val Lys Phe Gln Arg Ile Tyr Gln PheAla Arg 865 870 875 880 ctt aat tac acc aaa gga gcc aca tcc agt aaa ccagaa aca ccc gga 2688 Leu Asn Tyr Thr Lys Gly Ala Thr Ser Ser Lys Pro GluThr Pro Gly 885 890 895 gtc tat gac atg gat ggt aga aat agc aat aca ctcctt aat ttg gat 2736 Val Tyr Asp Met Asp Gly Arg Asn Ser Asn Thr Leu LeuAsn Leu Asp 900 905 910 cct gaa aat gtt gta ttt tat gtt gga ggt tac ccacct gat ttt aaa 2784 Pro Glu Asn Val Val Phe Tyr Val Gly Gly Tyr Pro ProAsp Phe Lys 915 920 925 ctt ccc agt cga cta agt ttc cct cca tac aaa ggttgt att gaa tta 2832 Leu Pro Ser Arg Leu Ser Phe Pro Pro Tyr Lys Gly CysIle Glu Leu 930 935 940 gat gac ctc aat gaa aat gtt ctg agc ttg tac aacttc aaa aaa aca 2880 Asp Asp Leu Asn Glu Asn Val Leu Ser Leu Tyr Asn PheLys Lys Thr 945 950 955 960 ttc aat ctc aac aca act gaa gtg gag cct tgtaga agg agg aag gaa 2928 Phe Asn Leu Asn Thr Thr Glu Val Glu Pro Cys ArgArg Arg Lys Glu 965 970 975 gag tca gac aaa aat tat ttt gaa ggt acg ggctat gct cga gtt cca 2976 Glu Ser Asp Lys Asn Tyr Phe Glu Gly Thr Gly TyrAla Arg Val Pro 980 985 990 act caa cca cat gct ccc atc cca acc ttt ggacag aca att cag acc 3024 Thr Gln Pro His Ala Pro Ile Pro Thr Phe Gly GlnThr Ile Gln Thr 995 1000 1005 acc gtg gat aga ggc ttg ctg ttc ttt gcagaa aac ggg gat cgc ttc 3072 Thr Val Asp Arg Gly Leu Leu Phe Phe Ala GluAsn Gly Asp Arg Phe 1010 1015 1020 ata tct cta aat ata gaa gat ggc aagctc atg gtg aga tac aaa ctg 3120 Ile Ser Leu Asn Ile Glu Asp Gly Lys LeuMet Val Arg Tyr Lys Leu 1025 1030 1035 1040 aat tca gag cta cca aaa gagaga gga gtt gga gac gcc ata aac aac 3168 Asn Ser Glu Leu Pro Lys Glu ArgGly Val Gly Asp Ala Ile Asn Asn 1045 1050 1055 ggc aga gac cat tcg attcag atc aaa att gga aaa ctc caa aag cgt 3216 Gly Arg Asp His Ser Ile GlnIle Lys Ile Gly Lys Leu Gln Lys Arg 1060 1065 1070 atg tgg ata aat gtggac gtt caa aac act ata att gat ggt gaa gta 3264 Met Trp Ile Asn Val AspVal Gln Asn Thr Ile Ile Asp Gly Glu Val 1075 1080 1085 ttt gat ttc agcaca tat tat ctg gga gga att cca att gca atc agg 3312 Phe Asp Phe Ser ThrTyr Tyr Leu Gly Gly Ile Pro Ile Ala Ile Arg 1090 1095 1100 gaa aga tttaac att tct acg cct gct ttc cga ggc tgc atg aaa aat 3360 Glu Arg Phe AsnIle Ser Thr Pro Ala Phe Arg Gly Cys Met Lys Asn 1105 1110 1115 1120 ttgaag aaa acc agt ggt gtc gtt aga ttg aat gat act gtg gga gta 3408 Leu LysLys Thr Ser Gly Val Val Arg Leu Asn Asp Thr Val Gly Val 1125 1130 1135acc aaa aag tgc tcg gaa gac tgg aag ctt gtg cga tct gcc tca ttc 3456 ThrLys Lys Cys Ser Glu Asp Trp Lys Leu Val Arg Ser Ala Ser Phe 1140 11451150 tcc aga gga gga caa ttg agt ttc act gat ttg ggc tta cca cct act3504 Ser Arg Gly Gly Gln Leu Ser Phe Thr Asp Leu Gly Leu Pro Pro Thr1155 1160 1165 gac cac ctc cag gcc tca ttt gga ttt cag acc ttt caa cccagt ggc 3552 Asp His Leu Gln Ala Ser Phe Gly Phe Gln Thr Phe Gln Pro SerGly 1170 1175 1180 ata tta tta gat cat cag aca tgg aca agg aac ctg caggtc act ctg 3600 Ile Leu Leu Asp His Gln Thr Trp Thr Arg Asn Leu Gln ValThr Leu 1185 1190 1195 1200 gaa gat ggt tac att gaa ttg agc acc agc gatagc ggc ggc cca att 3648 Glu Asp Gly Tyr Ile Glu Leu Ser Thr Ser Asp SerGly Gly Pro Ile 1205 1210 1215 ttt aaa tct cca cag acg tat atg gat ggttta ctg cat tat gta tct 3696 Phe Lys Ser Pro Gln Thr Tyr Met Asp Gly LeuLeu His Tyr Val Ser 1220 1225 1230 gta ata agc gac aac tct gga cta cggctt ctc atc gat gac cag ctt 3744 Val Ile Ser Asp Asn Ser Gly Leu Arg LeuLeu Ile Asp Asp Gln Leu 1235 1240 1245 ctg aga aat agc aaa agg cta aaacac att tca agt tcc cgg cag tct 3792 Leu Arg Asn Ser Lys Arg Leu Lys HisIle Ser Ser Ser Arg Gln Ser 1250 1255 1260 ctg cgt ctg ggc ggg agc aatttt gag ggt tgt att agc aat gtt ttt 3840 Leu Arg Leu Gly Gly Ser Asn PheGlu Gly Cys Ile Ser Asn Val Phe 1265 1270 1275 1280 gtc cag agg tta tcactg agt cct gaa gtc cta gat ttg acc agt aac 3888 Val Gln Arg Leu Ser LeuSer Pro Glu Val Leu Asp Leu Thr Ser Asn 1285 1290 1295 tct ctc aag agagat gtg tcc ctg gga ggc tgc agt tta aac aaa cca 3936 Ser Leu Lys Arg AspVal Ser Leu Gly Gly Cys Ser Leu Asn Lys Pro 1300 1305 1310 cct ttt ctaatg ttg ctt aaa ggt tct acc agg ttt aac aag acc aag 3984 Pro Phe Leu MetLeu Leu Lys Gly Ser Thr Arg Phe Asn Lys Thr Lys 1315 1320 1325 act tttcgt atc aac cag ctg ttg cag gac aca cca gtg gcc tcc cca 4032 Thr Phe ArgIle Asn Gln Leu Leu Gln Asp Thr Pro Val Ala Ser Pro 1330 1335 1340 aggagc gtg aag gtg tgg caa gat gct tgc tca cca ctt ccc aag acc 4080 Arg SerVal Lys Val Trp Gln Asp Ala Cys Ser Pro Leu Pro Lys Thr 1345 1350 13551360 cag gcc aat cat gga gcc ctc cag ttt ggg gac att ccc acc agc cac4128 Gln Ala Asn His Gly Ala Leu Gln Phe Gly Asp Ile Pro Thr Ser His1365 1370 1375 ttg cta ttc aag ctt cct cag gag ctg ctg aaa ccc agg tcacag ttt 4176 Leu Leu Phe Lys Leu Pro Gln Glu Leu Leu Lys Pro Arg Ser GlnPhe 1380 1385 1390 gct gtg gac atg cag aca aca tcc tcc aga gga ctg gtgttt cac acg 4224 Ala Val Asp Met Gln Thr Thr Ser Ser Arg Gly Leu Val PheHis Thr 1395 1400 1405 ggc act aag aac tcc ttt atg gct ctt tat ctt tcaaaa gga cgt ctg 4272 Gly Thr Lys Asn Ser Phe Met Ala Leu Tyr Leu Ser LysGly Arg Leu 1410 1415 1420 gtc ttt gca ctg ggg aca gat ggg aaa aaa ttgagg atc aaa agc aag 4320 Val Phe Ala Leu Gly Thr Asp Gly Lys Lys Leu ArgIle Lys Ser Lys 1425 1430 1435 1440 gag aaa tgc aat gat ggg aaa tgg cacacg gtg gtg ttt ggc cat gat 4368 Glu Lys Cys Asn Asp Gly Lys Trp His ThrVal Val Phe Gly His Asp 1445 1450 1455 ggg gaa aag ggg cgc ttg gtt gtggat gga ctg agg gcc cgg gag gga 4416 Gly Glu Lys Gly Arg Leu Val Val AspGly Leu Arg Ala Arg Glu Gly 1460 1465 1470 agt ttg cct gga aac tcc accatc agc atc aga gcg cca gtt tac ctg 4464 Ser Leu Pro Gly Asn Ser Thr IleSer Ile Arg Ala Pro Val Tyr Leu 1475 1480 1485 gga tca cct cca tca gggaaa cca aag agc ctc ccc aca aac agc ttt 4512 Gly Ser Pro Pro Ser Gly LysPro Lys Ser Leu Pro Thr Asn Ser Phe 1490 1495 1500 gtg gga tgc ctg aagaac ttt cag ctg gat tca aaa ccc ttg tat acc 4560 Val Gly Cys Leu Lys AsnPhe Gln Leu Asp Ser Lys Pro Leu Tyr Thr 1505 1510 1515 1520 cct tct tcaagc ttc ggg gtg tct tcc tgc ttg ggt ggt cct ttg gag 4608 Pro Ser Ser SerPhe Gly Val Ser Ser Cys Leu Gly Gly Pro Leu Glu 1525 1530 1535 aaa ggcatt tat ttc tct gaa gaa gga ggt cat gtc gtc ttg gct cac 4656 Lys Gly IleTyr Phe Ser Glu Glu Gly Gly His Val Val Leu Ala His 1540 1545 1550 tctgta ttg ttg ggg cca gaa ttt aag ctt gtt ttc agc atc cgc cca 4704 Ser ValLeu Leu Gly Pro Glu Phe Lys Leu Val Phe Ser Ile Arg Pro 1555 1560 1565aga agt ctc act ggg atc cta ata cac atc gga agt cag ccc ggg aag 4752 ArgSer Leu Thr Gly Ile Leu Ile His Ile Gly Ser Gln Pro Gly Lys 1570 15751580 cac tta tgt gtt tac ctg gag gca gga aag gtc acg gcc tct atg gac4800 His Leu Cys Val Tyr Leu Glu Ala Gly Lys Val Thr Ala Ser Met Asp1585 1590 1595 1600 agt ggg gca ggt ggg acc tca acg tcg gtc aca cca aagcag tct ctg 4848 Ser Gly Ala Gly Gly Thr Ser Thr Ser Val Thr Pro Lys GlnSer Leu 1605 1610 1615 tgt gat gga cag tgg cac tcg gtg gca gtc acc ataaaa caa cac atc 4896 Cys Asp Gly Gln Trp His Ser Val Ala Val Thr Ile LysGln His Ile 1620 1625 1630 ctg cac ctg gaa ctg gac aca gac agt agc tacaca gct gga cag atc 4944 Leu His Leu Glu Leu Asp Thr Asp Ser Ser Tyr ThrAla Gly Gln Ile 1635 1640 1645 ccc ttc cca cct gcc agc act caa gag ccacta cac ctt gga ggt gct 4992 Pro Phe Pro Pro Ala Ser Thr Gln Glu Pro LeuHis Leu Gly Gly Ala 1650 1655 1660 cca gcc aat ttg acg aca ctg agg atccct gtg tgg aaa tca ttc ttt 5040 Pro Ala Asn Leu Thr Thr Leu Arg Ile ProVal Trp Lys Ser Phe Phe 1665 1670 1675 1680 ggc tgt ctg agg aat att catgtc aat cac atc cct gtc cct gtc act 5088 Gly Cys Leu Arg Asn Ile His ValAsn His Ile Pro Val Pro Val Thr 1685 1690 1695 gaa gcc ttg gaa gtc cagggg cct gtc agt ctg aat ggt tgt cct gac 5136 Glu Ala Leu Glu Val Gln GlyPro Val Ser Leu Asn Gly Cys Pro Asp 1700 1705 1710 cag taacccaagcctatttcaca gcaaggaaat tcaccttcaa aagcactgat 5189 Gln tacccaatgcacctccctcc ccagctcgag atcattcttc aattaggaca caaaccagac 5249 aggtttaatagcgaatctaa ttttgaattc tgaccatgga tacccatcac tttggcattc 5309 agtgctacatgtgtatttta tataaaaatc ccatttcttg aagataaaaa aattgttatt 5369 caaattgttatgcacagaat gtttttggta atattaattt ccactaaaaa attaaatgtc 5429 tttt 5433 61713 PRT Homo sapiens 6 Met Gly Trp Leu Trp Ile Phe Gly Ala Ala Leu GlyGln Cys Leu Gly 1 5 10 15 Tyr Ser Ser Gln Gln Gln Arg Val Pro Phe LeuGln Pro Pro Gly Gln 20 25 30 Ser Gln Leu Gln Ala Ser Tyr Val Glu Phe ArgPro Ser Gln Gly Cys 35 40 45 Ser Pro Gly Tyr Tyr Arg Asp His Lys Gly LeuTyr Thr Gly Arg Cys 50 55 60 Val Pro Cys Asn Cys Asn Gly His Ser Asn GlnCys Gln Asp Gly Ser 65 70 75 80 Gly Ile Cys Val Asn Cys Gln His Asn ThrAla Gly Glu His Cys Glu 85 90 95 Arg Cys Gln Glu Gly Tyr Tyr Gly Asn AlaVal His Gly Ser Cys Arg 100 105 110 Ala Cys Pro Cys Pro His Thr Asn SerPhe Ala Thr Gly Cys Val Val 115 120 125 Asn Gly Gly Asp Val Arg Cys SerCys Lys Ala Gly Tyr Thr Gly Thr 130 135 140 Gln Cys Glu Arg Cys Ala ProGly Tyr Phe Gly Asn Pro Gln Lys Phe 145 150 155 160 Gly Gly Ser Cys GlnPro Cys Ser Cys Asn Ser Asn Gly Gln Leu Gly 165 170 175 Ser Cys His ProLeu Thr Gly Asp Cys Ile Asn Gln Glu Pro Lys Asp 180 185 190 Ser Ser ProAla Glu Glu Cys Asp Asp Cys Asp Ser Cys Val Met Thr 195 200 205 Leu LeuAsn Asp Leu Ala Thr Met Gly Glu Gln Leu Arg Leu Val Lys 210 215 220 SerGln Leu Gln Gly Leu Ser Ala Ser Ala Gly Leu Leu Glu Gln Met 225 230 235240 Arg His Met Glu Thr Gln Ala Lys Asp Leu Arg Asn Gln Leu Leu Asn 245250 255 Tyr Arg Ser Ala Ile Ser Asn His Gly Ser Lys Ile Glu Gly Leu Glu260 265 270 Arg Glu Leu Thr Asp Leu Asn Gln Glu Phe Glu Thr Leu Gln GluLys 275 280 285 Ala Gln Val Asn Ser Arg Lys Ala Gln Thr Leu Asn Asn AsnVal Asn 290 295 300 Arg Ala Thr Gln Ser Ala Lys Glu Leu Asp Val Lys IleLys Asn Val 305 310 315 320 Ile Arg Asn Val His Ile Leu Leu Lys Gln IleSer Gly Thr Asp Gly 325 330 335 Glu Gly Asn Asn Val Pro Ser Gly Asp PheSer Arg Glu Trp Ala Glu 340 345 350 Ala Gln Arg Met Met Arg Glu Leu ArgAsn Arg Asn Phe Gly Lys His 355 360 365 Leu Arg Glu Ala Glu Ala Asp LysArg Glu Ser Gln Leu Leu Leu Asn 370 375 380 Arg Ile Arg Thr Trp Gln LysThr His Gln Gly Glu Asn Asn Gly Leu 385 390 395 400 Ala Asn Ser Ile ArgAsp Ser Leu Asn Glu Tyr Glu Ala Lys Leu Ser 405 410 415 Asp Leu Arg AlaArg Leu Gln Glu Ala Ala Ala Gln Ala Lys Gln Ala 420 425 430 Asn Gly LeuAsn Gln Glu Asn Glu Arg Ala Leu Gly Ala Ile Gln Arg 435 440 445 Gln ValLys Glu Ile Asn Ser Leu Gln Ser Asp Phe Thr Lys Tyr Leu 450 455 460 ThrThr Ala Asp Ser Ser Leu Leu Gln Thr Asn Ile Ala Leu Gln Leu 465 470 475480 Met Glu Lys Ser Gln Lys Glu Tyr Glu Lys Leu Ala Ala Ser Leu Asn 485490 495 Glu Ala Arg Gln Glu Leu Ser Asp Lys Val Arg Glu Leu Ser Arg Ser500 505 510 Ala Gly Lys Thr Ser Leu Val Glu Glu Ala Glu Lys His Ala ArgSer 515 520 525 Leu Gln Glu Leu Ala Lys Gln Leu Glu Glu Ile Lys Arg AsnAla Ser 530 535 540 Gly Asp Glu Leu Val Arg Cys Ala Val Asp Ala Ala ThrAla Tyr Glu 545 550 555 560 Asn Ile Leu Asn Ala Ile Lys Ala Ala Glu AspAla Ala Asn Arg Ala 565 570 575 Ala Ser Ala Ser Glu Ser Ala Leu Gln ThrVal Ile Lys Glu Asp Leu 580 585 590 Pro Arg Lys Ala Lys Thr Leu Ser SerAsn Ser Asp Lys Leu Leu Asn 595 600 605 Glu Ala Lys Met Thr Gln Lys LysLeu Lys Gln Glu Val Ser Pro Ala 610 615 620 Leu Asn Asn Leu Gln Gln ThrLeu Asn Ile Val Thr Val Gln Lys Glu 625 630 635 640 Val Ile Asp Thr AsnLeu Thr Thr Leu Arg Asp Gly Leu His Gly Ile 645 650 655 Gln Arg Gly AspIle Asp Ala Met Ile Ser Ser Ala Lys Ser Met Val 660 665 670 Arg Lys AlaAsn Asp Ile Thr Asp Glu Val Leu Asp Gly Leu Asn Pro 675 680 685 Ile GlnThr Asp Val Glu Arg Ile Lys Asp Thr Tyr Gly Arg Thr Gln 690 695 700 AsnGlu Asp Phe Lys Lys Ala Leu Thr Asp Ala Asp Asn Ser Val Asn 705 710 715720 Lys Leu Thr Asn Lys Leu Pro Asp Leu Trp Arg Lys Ile Glu Ser Ile 725730 735 Asn Gln Gln Leu Leu Pro Leu Gly Asn Ile Ser Asp Asn Met Asp Arg740 745 750 Ile Arg Glu Leu Ile Gln Gln Ala Arg Asp Ala Ala Ser Lys ValAla 755 760 765 Val Pro Met Arg Phe Asn Gly Lys Ser Gly Val Glu Val ArgLeu Pro 770 775 780 Asn Asp Leu Glu Asp Leu Lys Gly Tyr Thr Ser Leu SerLeu Phe Leu 785 790 795 800 Gln Arg Pro Asn Ser Arg Glu Asn Gly Gly ThrGlu Asn Met Phe Val 805 810 815 Met Tyr Leu Gly Asn Lys Asp Ala Ser ArgAsp Tyr Ile Gly Met Ala 820 825 830 Val Val Asp Gly Gln Leu Thr Cys ValTyr Asn Leu Gly Asp Arg Glu 835 840 845 Ala Glu Leu Gln Val Asp Gln IleLeu Thr Lys Ser Glu Thr Lys Glu 850 855 860 Ala Val Met Asp Arg Val LysPhe Gln Arg Ile Tyr Gln Phe Ala Arg 865 870 875 880 Leu Asn Tyr Thr LysGly Ala Thr Ser Ser Lys Pro Glu Thr Pro Gly 885 890 895 Val Tyr Asp MetAsp Gly Arg Asn Ser Asn Thr Leu Leu Asn Leu Asp 900 905 910 Pro Glu AsnVal Val Phe Tyr Val Gly Gly Tyr Pro Pro Asp Phe Lys 915 920 925 Leu ProSer Arg Leu Ser Phe Pro Pro Tyr Lys Gly Cys Ile Glu Leu 930 935 940 AspAsp Leu Asn Glu Asn Val Leu Ser Leu Tyr Asn Phe Lys Lys Thr 945 950 955960 Phe Asn Leu Asn Thr Thr Glu Val Glu Pro Cys Arg Arg Arg Lys Glu 965970 975 Glu Ser Asp Lys Asn Tyr Phe Glu Gly Thr Gly Tyr Ala Arg Val Pro980 985 990 Thr Gln Pro His Ala Pro Ile Pro Thr Phe Gly Gln Thr Ile GlnThr 995 1000 1005 Thr Val Asp Arg Gly Leu Leu Phe Phe Ala Glu Asn GlyAsp Arg Phe 1010 1015 1020 Ile Ser Leu Asn Ile Glu Asp Gly Lys Leu MetVal Arg Tyr Lys Leu 1025 1030 1035 1040 Asn Ser Glu Leu Pro Lys Glu ArgGly Val Gly Asp Ala Ile Asn Asn 1045 1050 1055 Gly Arg Asp His Ser IleGln Ile Lys Ile Gly Lys Leu Gln Lys Arg 1060 1065 1070 Met Trp Ile AsnVal Asp Val Gln Asn Thr Ile Ile Asp Gly Glu Val 1075 1080 1085 Phe AspPhe Ser Thr Tyr Tyr Leu Gly Gly Ile Pro Ile Ala Ile Arg 1090 1095 1100Glu Arg Phe Asn Ile Ser Thr Pro Ala Phe Arg Gly Cys Met Lys Asn 11051110 1115 1120 Leu Lys Lys Thr Ser Gly Val Val Arg Leu Asn Asp Thr ValGly Val 1125 1130 1135 Thr Lys Lys Cys Ser Glu Asp Trp Lys Leu Val ArgSer Ala Ser Phe 1140 1145 1150 Ser Arg Gly Gly Gln Leu Ser Phe Thr AspLeu Gly Leu Pro Pro Thr 1155 1160 1165 Asp His Leu Gln Ala Ser Phe GlyPhe Gln Thr Phe Gln Pro Ser Gly 1170 1175 1180 Ile Leu Leu Asp His GlnThr Trp Thr Arg Asn Leu Gln Val Thr Leu 1185 1190 1195 1200 Glu Asp GlyTyr Ile Glu Leu Ser Thr Ser Asp Ser Gly Gly Pro Ile 1205 1210 1215 PheLys Ser Pro Gln Thr Tyr Met Asp Gly Leu Leu His Tyr Val Ser 1220 12251230 Val Ile Ser Asp Asn Ser Gly Leu Arg Leu Leu Ile Asp Asp Gln Leu1235 1240 1245 Leu Arg Asn Ser Lys Arg Leu Lys His Ile Ser Ser Ser ArgGln Ser 1250 1255 1260 Leu Arg Leu Gly Gly Ser Asn Phe Glu Gly Cys IleSer Asn Val Phe 1265 1270 1275 1280 Val Gln Arg Leu Ser Leu Ser Pro GluVal Leu Asp Leu Thr Ser Asn 1285 1290 1295 Ser Leu Lys Arg Asp Val SerLeu Gly Gly Cys Ser Leu Asn Lys Pro 1300 1305 1310 Pro Phe Leu Met LeuLeu Lys Gly Ser Thr Arg Phe Asn Lys Thr Lys 1315 1320 1325 Thr Phe ArgIle Asn Gln Leu Leu Gln Asp Thr Pro Val Ala Ser Pro 1330 1335 1340 ArgSer Val Lys Val Trp Gln Asp Ala Cys Ser Pro Leu Pro Lys Thr 1345 13501355 1360 Gln Ala Asn His Gly Ala Leu Gln Phe Gly Asp Ile Pro Thr SerHis 1365 1370 1375 Leu Leu Phe Lys Leu Pro Gln Glu Leu Leu Lys Pro ArgSer Gln Phe 1380 1385 1390 Ala Val Asp Met Gln Thr Thr Ser Ser Arg GlyLeu Val Phe His Thr 1395 1400 1405 Gly Thr Lys Asn Ser Phe Met Ala LeuTyr Leu Ser Lys Gly Arg Leu 1410 1415 1420 Val Phe Ala Leu Gly Thr AspGly Lys Lys Leu Arg Ile Lys Ser Lys 1425 1430 1435 1440 Glu Lys Cys AsnAsp Gly Lys Trp His Thr Val Val Phe Gly His Asp 1445 1450 1455 Gly GluLys Gly Arg Leu Val Val Asp Gly Leu Arg Ala Arg Glu Gly 1460 1465 1470Ser Leu Pro Gly Asn Ser Thr Ile Ser Ile Arg Ala Pro Val Tyr Leu 14751480 1485 Gly Ser Pro Pro Ser Gly Lys Pro Lys Ser Leu Pro Thr Asn SerPhe 1490 1495 1500 Val Gly Cys Leu Lys Asn Phe Gln Leu Asp Ser Lys ProLeu Tyr Thr 1505 1510 1515 1520 Pro Ser Ser Ser Phe Gly Val Ser Ser CysLeu Gly Gly Pro Leu Glu 1525 1530 1535 Lys Gly Ile Tyr Phe Ser Glu GluGly Gly His Val Val Leu Ala His 1540 1545 1550 Ser Val Leu Leu Gly ProGlu Phe Lys Leu Val Phe Ser Ile Arg Pro 1555 1560 1565 Arg Ser Leu ThrGly Ile Leu Ile His Ile Gly Ser Gln Pro Gly Lys 1570 1575 1580 His LeuCys Val Tyr Leu Glu Ala Gly Lys Val Thr Ala Ser Met Asp 1585 1590 15951600 Ser Gly Ala Gly Gly Thr Ser Thr Ser Val Thr Pro Lys Gln Ser Leu1605 1610 1615 Cys Asp Gly Gln Trp His Ser Val Ala Val Thr Ile Lys GlnHis Ile 1620 1625 1630 Leu His Leu Glu Leu Asp Thr Asp Ser Ser Tyr ThrAla Gly Gln Ile 1635 1640 1645 Pro Phe Pro Pro Ala Ser Thr Gln Glu ProLeu His Leu Gly Gly Ala 1650 1655 1660 Pro Ala Asn Leu Thr Thr Leu ArgIle Pro Val Trp Lys Ser Phe Phe 1665 1670 1675 1680 Gly Cys Leu Arg AsnIle His Val Asn His Ile Pro Val Pro Val Thr 1685 1690 1695 Glu Ala LeuGlu Val Gln Gly Pro Val Ser Leu Asn Gly Cys Pro Asp 1700 1705 1710 Gln 75373 DNA Homo sapiens CDS (1)..(5079) 7 cag caa agg gtg cca ttt ctt cagcct ccc ggt caa agt caa ctg caa 48 Gln Gln Arg Val Pro Phe Leu Gln ProPro Gly Gln Ser Gln Leu Gln 1 5 10 15 gcg agt tat gtg gag ttt aga cccagc cag ggt tgt agc cct gga tac 96 Ala Ser Tyr Val Glu Phe Arg Pro SerGln Gly Cys Ser Pro Gly Tyr 20 25 30 tat cgg gat cat aaa ggc ttg tat accgga cgg tgt gtt ccc tgc aat 144 Tyr Arg Asp His Lys Gly Leu Tyr Thr GlyArg Cys Val Pro Cys Asn 35 40 45 tgc aac gga cat tca aat caa tgc cag gatggc tca ggc ata tgt gtt 192 Cys Asn Gly His Ser Asn Gln Cys Gln Asp GlySer Gly Ile Cys Val 50 55 60 aac tgt cag cac aac acc gcg gga gag cac tgtgaa cgc tgc cag gag 240 Asn Cys Gln His Asn Thr Ala Gly Glu His Cys GluArg Cys Gln Glu 65 70 75 80 ggc tac tat ggc aac gcc gtc cac gga tcc tgcagg gcc tgc cca tgt 288 Gly Tyr Tyr Gly Asn Ala Val His Gly Ser Cys ArgAla Cys Pro Cys 85 90 95 cct cac act aac agc ttt gcc act ggc tgt gtg gtgaat ggg gga gac 336 Pro His Thr Asn Ser Phe Ala Thr Gly Cys Val Val AsnGly Gly Asp 100 105 110 gtg cgg tgc tcc tgc aaa gct ggg tac aca gga acacag tgt gaa agg 384 Val Arg Cys Ser Cys Lys Ala Gly Tyr Thr Gly Thr GlnCys Glu Arg 115 120 125 tgt gca ccg gga tat ttc ggg aat ccc cag aaa ttcgga ggt agc tgc 432 Cys Ala Pro Gly Tyr Phe Gly Asn Pro Gln Lys Phe GlyGly Ser Cys 130 135 140 caa cca tgc agt tgt aac agc aat ggc cag ctg ggcagc tgt cat ccc 480 Gln Pro Cys Ser Cys Asn Ser Asn Gly Gln Leu Gly SerCys His Pro 145 150 155 160 ctg act gga gac tgc ata aac caa gaa ccc aaagat agc agc cct gca 528 Leu Thr Gly Asp Cys Ile Asn Gln Glu Pro Lys AspSer Ser Pro Ala 165 170 175 gaa gaa tgt gat gat tgc gac agc tgt gtg atgacc ctc ctg aac gac 576 Glu Glu Cys Asp Asp Cys Asp Ser Cys Val Met ThrLeu Leu Asn Asp 180 185 190 ctg gcc acc atg ggc gag cag ctc cgc ctg gtcaag tct cag ctg cag 624 Leu Ala Thr Met Gly Glu Gln Leu Arg Leu Val LysSer Gln Leu Gln 195 200 205 ggc ctg agt gcc agc gca ggg ctt ctg gag cagatg agg cac atg gag 672 Gly Leu Ser Ala Ser Ala Gly Leu Leu Glu Gln MetArg His Met Glu 210 215 220 acc cag gcc aag gac ctg agg aat cag ttg ctcaac tac cgt tct gcc 720 Thr Gln Ala Lys Asp Leu Arg Asn Gln Leu Leu AsnTyr Arg Ser Ala 225 230 235 240 att tca aat cat gga tca aaa ata gaa ggcctg gaa aga gaa ctg act 768 Ile Ser Asn His Gly Ser Lys Ile Glu Gly LeuGlu Arg Glu Leu Thr 245 250 255 gat ttg aat caa gaa ttt gag act ttg caagaa aag gct caa gta aat 816 Asp Leu Asn Gln Glu Phe Glu Thr Leu Gln GluLys Ala Gln Val Asn 260 265 270 tcc aga aaa gca caa aca tta aac aac aatgtt aat cgg gca aca caa 864 Ser Arg Lys Ala Gln Thr Leu Asn Asn Asn ValAsn Arg Ala Thr Gln 275 280 285 agc gca aaa gaa ctg gat gtg aag att aaaaat gtc atc cgg aat gtg 912 Ser Ala Lys Glu Leu Asp Val Lys Ile Lys AsnVal Ile Arg Asn Val 290 295 300 cac att ctt tta aag cag atc tct ggg acagat gga gag gga aac aac 960 His Ile Leu Leu Lys Gln Ile Ser Gly Thr AspGly Glu Gly Asn Asn 305 310 315 320 gtg cct tca ggt gac ttt tcc aga gagtgg gct gaa gcc cag cgc atg 1008 Val Pro Ser Gly Asp Phe Ser Arg Glu TrpAla Glu Ala Gln Arg Met 325 330 335 atg agg gaa ctg cgg aac agg aac tttgga aag cac ctc aga gaa gca 1056 Met Arg Glu Leu Arg Asn Arg Asn Phe GlyLys His Leu Arg Glu Ala 340 345 350 gaa gct gat aaa agg gag tcg cag ctcttg ctg aac cgg ata agg acc 1104 Glu Ala Asp Lys Arg Glu Ser Gln Leu LeuLeu Asn Arg Ile Arg Thr 355 360 365 tgg cag aaa acc cac cag ggg gag aacaat ggg ctt gct aac agt atc 1152 Trp Gln Lys Thr His Gln Gly Glu Asn AsnGly Leu Ala Asn Ser Ile 370 375 380 cgg gat tct tta aat gaa tac gaa gccaaa ctc agt gac ctt cgt gct 1200 Arg Asp Ser Leu Asn Glu Tyr Glu Ala LysLeu Ser Asp Leu Arg Ala 385 390 395 400 cgg ctg cag gag gca gct gcc caagcc aag cag gca aat ggc ttg aac 1248 Arg Leu Gln Glu Ala Ala Ala Gln AlaLys Gln Ala Asn Gly Leu Asn 405 410 415 caa gaa aac gag aga gct ttg ggagcc att cag aga caa gtg aaa gaa 1296 Gln Glu Asn Glu Arg Ala Leu Gly AlaIle Gln Arg Gln Val Lys Glu 420 425 430 ata aat tcc ctg cag agt gat ttcacc aag tat cta acc act gca gac 1344 Ile Asn Ser Leu Gln Ser Asp Phe ThrLys Tyr Leu Thr Thr Ala Asp 435 440 445 tca tct ttg ttg caa acc aac attgcg ctg cag ctg atg gag aaa agc 1392 Ser Ser Leu Leu Gln Thr Asn Ile AlaLeu Gln Leu Met Glu Lys Ser 450 455 460 cag aag gaa tat gaa aaa tta gctgcc agt tta aat gaa gca aga caa 1440 Gln Lys Glu Tyr Glu Lys Leu Ala AlaSer Leu Asn Glu Ala Arg Gln 465 470 475 480 gaa cta agt gac aaa gta agagaa ctt tcc aga tct gct ggc aaa aca 1488 Glu Leu Ser Asp Lys Val Arg GluLeu Ser Arg Ser Ala Gly Lys Thr 485 490 495 tcc ctt gtg gag gag gca gaaaag cac gcg cgg tcc tta caa gag ctg 1536 Ser Leu Val Glu Glu Ala Glu LysHis Ala Arg Ser Leu Gln Glu Leu 500 505 510 gca aag cag ctg gaa gag atcaag aga aac gcc agc ggg gat gag ctg 1584 Ala Lys Gln Leu Glu Glu Ile LysArg Asn Ala Ser Gly Asp Glu Leu 515 520 525 gtg cgc tgt gct gtg gat gccgcc acc gcc tac gag aac atc ctc aat 1632 Val Arg Cys Ala Val Asp Ala AlaThr Ala Tyr Glu Asn Ile Leu Asn 530 535 540 gcc atc aaa gcg gcc gag gacgca gcc aac agg gct gcc agt gca tct 1680 Ala Ile Lys Ala Ala Glu Asp AlaAla Asn Arg Ala Ala Ser Ala Ser 545 550 555 560 gaa tct gcc ctc cag acagtg ata aag gaa gat ctg cca aga aaa gct 1728 Glu Ser Ala Leu Gln Thr ValIle Lys Glu Asp Leu Pro Arg Lys Ala 565 570 575 aaa acc ctg agt tcc aacagt gat aaa ctg tta aat gaa gcc aag atg 1776 Lys Thr Leu Ser Ser Asn SerAsp Lys Leu Leu Asn Glu Ala Lys Met 580 585 590 aca caa aag aag cta aagcaa gaa gtc agt cca gct ctc aac aac cta 1824 Thr Gln Lys Lys Leu Lys GlnGlu Val Ser Pro Ala Leu Asn Asn Leu 595 600 605 cag caa acc ctg aat attgtg aca gtt cag aaa gaa gtg ata gac acc 1872 Gln Gln Thr Leu Asn Ile ValThr Val Gln Lys Glu Val Ile Asp Thr 610 615 620 aat ctc aca act ctc cgagat ggt ctt cat ggg ata cag aga ggt gat 1920 Asn Leu Thr Thr Leu Arg AspGly Leu His Gly Ile Gln Arg Gly Asp 625 630 635 640 att gat gct atg atcagt agt gca aag agc atg gtc aga aag gcc aac 1968 Ile Asp Ala Met Ile SerSer Ala Lys Ser Met Val Arg Lys Ala Asn 645 650 655 gac atc aca gat gaggtt ctg gat ggg ctc aac ccc atc cag aca gat 2016 Asp Ile Thr Asp Glu ValLeu Asp Gly Leu Asn Pro Ile Gln Thr Asp 660 665 670 gtg gaa aga att aaggac acc tat ggg agg aca cag aac gaa gac ttc 2064 Val Glu Arg Ile Lys AspThr Tyr Gly Arg Thr Gln Asn Glu Asp Phe 675 680 685 aaa aag gct ctg actgat gca gat aac tcg gtg aat aag tta acc aac 2112 Lys Lys Ala Leu Thr AspAla Asp Asn Ser Val Asn Lys Leu Thr Asn 690 695 700 aaa cta cct gat ctttgg cgc aag att gaa agt atc aac caa cag ctg 2160 Lys Leu Pro Asp Leu TrpArg Lys Ile Glu Ser Ile Asn Gln Gln Leu 705 710 715 720 ttg ccc ttg ggaaac atc tct gac aac atg gac aga ata cga gaa cta 2208 Leu Pro Leu Gly AsnIle Ser Asp Asn Met Asp Arg Ile Arg Glu Leu 725 730 735 att cag cag gccaga gat gct gcc agt aag gtt gct gtc ccc atg agg 2256 Ile Gln Gln Ala ArgAsp Ala Ala Ser Lys Val Ala Val Pro Met Arg 740 745 750 ttc aat ggt aaatct gga gtc gaa gtc cga ctg cca aat gac ctg gaa 2304 Phe Asn Gly Lys SerGly Val Glu Val Arg Leu Pro Asn Asp Leu Glu 755 760 765 gat ttg aaa ggatat aca tct ctg tcc ttg ttt ctc caa agg ccc aac 2352 Asp Leu Lys Gly TyrThr Ser Leu Ser Leu Phe Leu Gln Arg Pro Asn 770 775 780 tca aga gaa aatggg ggt act gag aat atg ttt gtg atg tac ctt gga 2400 Ser Arg Glu Asn GlyGly Thr Glu Asn Met Phe Val Met Tyr Leu Gly 785 790 795 800 aat aaa gatgcc tcc cgg gac tac atc ggc atg gca gtt gtg gat ggc 2448 Asn Lys Asp AlaSer Arg Asp Tyr Ile Gly Met Ala Val Val Asp Gly 805 810 815 cag ctc acctgt gtc tac aac ctg ggg gac cgt gag gct gaa ctc caa 2496 Gln Leu Thr CysVal Tyr Asn Leu Gly Asp Arg Glu Ala Glu Leu Gln 820 825 830 gtg gac cagatc ttg acc aag agt gag act aag gag gca gtt atg gat 2544 Val Asp Gln IleLeu Thr Lys Ser Glu Thr Lys Glu Ala Val Met Asp 835 840 845 cgg gtg aaattt cag aga att tat cag ttt gca agg ctt aat tac acc 2592 Arg Val Lys PheGln Arg Ile Tyr Gln Phe Ala Arg Leu Asn Tyr Thr 850 855 860 aaa gga gccaca tcc agt aaa cca gaa aca ccc gga gtc tat gac atg 2640 Lys Gly Ala ThrSer Ser Lys Pro Glu Thr Pro Gly Val Tyr Asp Met 865 870 875 880 gat ggtaga aat agc aat aca ctc ctt aat ttg gat cct gaa aat gtt 2688 Asp Gly ArgAsn Ser Asn Thr Leu Leu Asn Leu Asp Pro Glu Asn Val 885 890 895 gta ttttat gtt gga ggt tac cca cct gat ttt aaa ctt ccc agt cga 2736 Val Phe TyrVal Gly Gly Tyr Pro Pro Asp Phe Lys Leu Pro Ser Arg 900 905 910 cta agtttc cct cca tac aaa ggt tgt att gaa tta gat gac ctc aat 2784 Leu Ser PhePro Pro Tyr Lys Gly Cys Ile Glu Leu Asp Asp Leu Asn 915 920 925 gaa aatgtt ctg agc ttg tac aac ttc aaa aaa aca ttc aat ctc aac 2832 Glu Asn ValLeu Ser Leu Tyr Asn Phe Lys Lys Thr Phe Asn Leu Asn 930 935 940 aca actgaa gtg gag cct tgt aga agg agg aag gaa gag tca gac aaa 2880 Thr Thr GluVal Glu Pro Cys Arg Arg Arg Lys Glu Glu Ser Asp Lys 945 950 955 960 aattat ttt gaa ggt acg ggc tat gct cga gtt cca act caa cca cat 2928 Asn TyrPhe Glu Gly Thr Gly Tyr Ala Arg Val Pro Thr Gln Pro His 965 970 975 gctccc atc cca acc ttt gga cag aca att cag acc acc gtg gat aga 2976 Ala ProIle Pro Thr Phe Gly Gln Thr Ile Gln Thr Thr Val Asp Arg 980 985 990 ggcttg ctg ttc ttt gca gaa aac ggg gat cgc ttc ata tct cta aat 3024 Gly LeuLeu Phe Phe Ala Glu Asn Gly Asp Arg Phe Ile Ser Leu Asn 995 1000 1005ata gaa gat ggc aag ctc atg gtg aga tac aaa ctg aat tca gag cta 3072 IleGlu Asp Gly Lys Leu Met Val Arg Tyr Lys Leu Asn Ser Glu Leu 1010 10151020 cca aaa gag aga gga gtt gga gac gcc ata aac aac ggc aga gac cat3120 Pro Lys Glu Arg Gly Val Gly Asp Ala Ile Asn Asn Gly Arg Asp His1025 1030 1035 1040 tcg att cag atc aaa att gga aaa ctc caa aag cgt atgtgg ata aat 3168 Ser Ile Gln Ile Lys Ile Gly Lys Leu Gln Lys Arg Met TrpIle Asn 1045 1050 1055 gtg gac gtt caa aac act ata att gat ggt gaa gtattt gat ttc agc 3216 Val Asp Val Gln Asn Thr Ile Ile Asp Gly Glu Val PheAsp Phe Ser 1060 1065 1070 aca tat tat ctg gga gga att cca att gca atcagg gaa aga ttt aac 3264 Thr Tyr Tyr Leu Gly Gly Ile Pro Ile Ala Ile ArgGlu Arg Phe Asn 1075 1080 1085 att tct acg cct gct ttc cga ggc tgc atgaaa aat ttg aag aaa acc 3312 Ile Ser Thr Pro Ala Phe Arg Gly Cys Met LysAsn Leu Lys Lys Thr 1090 1095 1100 agt ggt gtc gtt aga ttg aat gat actgtg gga gta acc aaa aag tgc 3360 Ser Gly Val Val Arg Leu Asn Asp Thr ValGly Val Thr Lys Lys Cys 1105 1110 1115 1120 tcg gaa gac tgg aag ctt gtgcga tct gcc tca ttc tcc aga gga gga 3408 Ser Glu Asp Trp Lys Leu Val ArgSer Ala Ser Phe Ser Arg Gly Gly 1125 1130 1135 caa ttg agt ttc act gatttg ggc tta cca cct act gac cac ctc cag 3456 Gln Leu Ser Phe Thr Asp LeuGly Leu Pro Pro Thr Asp His Leu Gln 1140 1145 1150 gcc tca ttt gga tttcag acc ttt caa ccc agt ggc ata tta tta gat 3504 Ala Ser Phe Gly Phe GlnThr Phe Gln Pro Ser Gly Ile Leu Leu Asp 1155 1160 1165 cat cag aca tggaca agg aac ctg cag gtc act ctg gaa gat ggt tac 3552 His Gln Thr Trp ThrArg Asn Leu Gln Val Thr Leu Glu Asp Gly Tyr 1170 1175 1180 att gaa ttgagc acc agc gat agc ggc ggc cca att ttt aaa tct cca 3600 Ile Glu Leu SerThr Ser Asp Ser Gly Gly Pro Ile Phe Lys Ser Pro 1185 1190 1195 1200 cagacg tat atg gat ggt tta ctg cat tat gta tct gta ata agc gac 3648 Gln ThrTyr Met Asp Gly Leu Leu His Tyr Val Ser Val Ile Ser Asp 1205 1210 1215aac tct gga cta cgg ctt ctc atc gat gac cag ctt ctg aga aat agc 3696 AsnSer Gly Leu Arg Leu Leu Ile Asp Asp Gln Leu Leu Arg Asn Ser 1220 12251230 aaa agg cta aaa cac att tca agt tcc cgg cag tct ctg cgt ctg ggc3744 Lys Arg Leu Lys His Ile Ser Ser Ser Arg Gln Ser Leu Arg Leu Gly1235 1240 1245 ggg agc aat ttt gag ggt tgt att agc aat gtt ttt gtc cagagg tta 3792 Gly Ser Asn Phe Glu Gly Cys Ile Ser Asn Val Phe Val Gln ArgLeu 1250 1255 1260 tca ctg agt cct gaa gtc cta gat ttg acc agt aac tctctc aag aga 3840 Ser Leu Ser Pro Glu Val Leu Asp Leu Thr Ser Asn Ser LeuLys Arg 1265 1270 1275 1280 gat gtg tcc ctg gga ggc tgc agt tta aac aaacca cct ttt cta atg 3888 Asp Val Ser Leu Gly Gly Cys Ser Leu Asn Lys ProPro Phe Leu Met 1285 1290 1295 ttg ctt aaa ggt tct acc agg ttt aac aagacc aag act ttt cgt atc 3936 Leu Leu Lys Gly Ser Thr Arg Phe Asn Lys ThrLys Thr Phe Arg Ile 1300 1305 1310 aac cag ctg ttg cag gac aca cca gtggcc tcc cca agg agc gtg aag 3984 Asn Gln Leu Leu Gln Asp Thr Pro Val AlaSer Pro Arg Ser Val Lys 1315 1320 1325 gtg tgg caa gat gct tgc tca ccactt ccc aag acc cag gcc aat cat 4032 Val Trp Gln Asp Ala Cys Ser Pro LeuPro Lys Thr Gln Ala Asn His 1330 1335 1340 gga gcc ctc cag ttt ggg gacatt ccc acc agc cac ttg cta ttc aag 4080 Gly Ala Leu Gln Phe Gly Asp IlePro Thr Ser His Leu Leu Phe Lys 1345 1350 1355 1360 ctt cct cag gag ctgctg aaa ccc agg tca cag ttt gct gtg gac atg 4128 Leu Pro Gln Glu Leu LeuLys Pro Arg Ser Gln Phe Ala Val Asp Met 1365 1370 1375 cag aca aca tcctcc aga gga ctg gtg ttt cac acg ggc act aag aac 4176 Gln Thr Thr Ser SerArg Gly Leu Val Phe His Thr Gly Thr Lys Asn 1380 1385 1390 tcc ttt atggct ctt tat ctt tca aaa gga cgt ctg gtc ttt gca ctg 4224 Ser Phe Met AlaLeu Tyr Leu Ser Lys Gly Arg Leu Val Phe Ala Leu 1395 1400 1405 ggg acagat ggg aaa aaa ttg agg atc aaa agc aag gag aaa tgc aat 4272 Gly Thr AspGly Lys Lys Leu Arg Ile Lys Ser Lys Glu Lys Cys Asn 1410 1415 1420 gatggg aaa tgg cac acg gtg gtg ttt ggc cat gat ggg gaa aag ggg 4320 Asp GlyLys Trp His Thr Val Val Phe Gly His Asp Gly Glu Lys Gly 1425 1430 14351440 cgc ttg gtt gtg gat gga ctg agg gcc cgg gag gga agt ttg cct gga4368 Arg Leu Val Val Asp Gly Leu Arg Ala Arg Glu Gly Ser Leu Pro Gly1445 1450 1455 aac tcc acc atc agc atc aga gcg cca gtt tac ctg gga tcacct cca 4416 Asn Ser Thr Ile Ser Ile Arg Ala Pro Val Tyr Leu Gly Ser ProPro 1460 1465 1470 tca ggg aaa cca aag agc ctc ccc aca aac agc ttt gtggga tgc ctg 4464 Ser Gly Lys Pro Lys Ser Leu Pro Thr Asn Ser Phe Val GlyCys Leu 1475 1480 1485 aag aac ttt cag ctg gat tca aaa ccc ttg tat acccct tct tca agc 4512 Lys Asn Phe Gln Leu Asp Ser Lys Pro Leu Tyr Thr ProSer Ser Ser 1490 1495 1500 ttc ggg gtg tct tcc tgc ttg ggt ggt cct ttggag aaa ggc att tat 4560 Phe Gly Val Ser Ser Cys Leu Gly Gly Pro Leu GluLys Gly Ile Tyr 1505 1510 1515 1520 ttc tct gaa gaa gga ggt cat gtc gtcttg gct cac tct gta ttg ttg 4608 Phe Ser Glu Glu Gly Gly His Val Val LeuAla His Ser Val Leu Leu 1525 1530 1535 ggg cca gaa ttt aag ctt gtt ttcagc atc cgc cca aga agt ctc act 4656 Gly Pro Glu Phe Lys Leu Val Phe SerIle Arg Pro Arg Ser Leu Thr 1540 1545 1550 ggg atc cta ata cac atc ggaagt cag ccc ggg aag cac tta tgt gtt 4704 Gly Ile Leu Ile His Ile Gly SerGln Pro Gly Lys His Leu Cys Val 1555 1560 1565 tac ctg gag gca gga aaggtc acg gcc tct atg gac agt ggg gca ggt 4752 Tyr Leu Glu Ala Gly Lys ValThr Ala Ser Met Asp Ser Gly Ala Gly 1570 1575 1580 ggg acc tca acg tcggtc aca cca aag cag tct ctg tgt gat gga cag 4800 Gly Thr Ser Thr Ser ValThr Pro Lys Gln Ser Leu Cys Asp Gly Gln 1585 1590 1595 1600 tgg cac tcggtg gca gtc acc ata aaa caa cac atc ctg cac ctg gaa 4848 Trp His Ser ValAla Val Thr Ile Lys Gln His Ile Leu His Leu Glu 1605 1610 1615 ctg gacaca gac agt agc tac aca gct gga cag atc ccc ttc cca cct 4896 Leu Asp ThrAsp Ser Ser Tyr Thr Ala Gly Gln Ile Pro Phe Pro Pro 1620 1625 1630 gccagc act caa gag cca cta cac ctt gga ggt gct cca gcc aat ttg 4944 Ala SerThr Gln Glu Pro Leu His Leu Gly Gly Ala Pro Ala Asn Leu 1635 1640 1645acg aca ctg agg atc cct gtg tgg aaa tca ttc ttt ggc tgt ctg agg 4992 ThrThr Leu Arg Ile Pro Val Trp Lys Ser Phe Phe Gly Cys Leu Arg 1650 16551660 aat att cat gtc aat cac atc cct gtc cct gtc act gaa gcc ttg gaa5040 Asn Ile His Val Asn His Ile Pro Val Pro Val Thr Glu Ala Leu Glu1665 1670 1675 1680 gtc cag ggg cct gtc agt ctg aat ggt tgt cct gac cagtaacccaagc 5089 Val Gln Gly Pro Val Ser Leu Asn Gly Cys Pro Asp Gln 16851690 ctatttcaca gcaaggaaat tcaccttcaa aagcactgat tacccaatgc acctccctcc5149 ccagctcgag atcattcttc aattaggaca caaaccagac aggtttaata gcgaatctaa5209 ttttgaattc tgaccatgga tacccatcac tttggcattc agtgctacat gtgtatttta5269 tataaaaatc ccatttcttg aagataaaaa aattgttatt caaattgtta tgcacagaat5329 gtttttggta atattaattt ccactaaaaa attaaatgtc tttt 5373 8 1693 PRTHomo sapiens 8 Gln Gln Arg Val Pro Phe Leu Gln Pro Pro Gly Gln Ser GlnLeu Gln 1 5 10 15 Ala Ser Tyr Val Glu Phe Arg Pro Ser Gln Gly Cys SerPro Gly Tyr 20 25 30 Tyr Arg Asp His Lys Gly Leu Tyr Thr Gly Arg Cys ValPro Cys Asn 35 40 45 Cys Asn Gly His Ser Asn Gln Cys Gln Asp Gly Ser GlyIle Cys Val 50 55 60 Asn Cys Gln His Asn Thr Ala Gly Glu His Cys Glu ArgCys Gln Glu 65 70 75 80 Gly Tyr Tyr Gly Asn Ala Val His Gly Ser Cys ArgAla Cys Pro Cys 85 90 95 Pro His Thr Asn Ser Phe Ala Thr Gly Cys Val ValAsn Gly Gly Asp 100 105 110 Val Arg Cys Ser Cys Lys Ala Gly Tyr Thr GlyThr Gln Cys Glu Arg 115 120 125 Cys Ala Pro Gly Tyr Phe Gly Asn Pro GlnLys Phe Gly Gly Ser Cys 130 135 140 Gln Pro Cys Ser Cys Asn Ser Asn GlyGln Leu Gly Ser Cys His Pro 145 150 155 160 Leu Thr Gly Asp Cys Ile AsnGln Glu Pro Lys Asp Ser Ser Pro Ala 165 170 175 Glu Glu Cys Asp Asp CysAsp Ser Cys Val Met Thr Leu Leu Asn Asp 180 185 190 Leu Ala Thr Met GlyGlu Gln Leu Arg Leu Val Lys Ser Gln Leu Gln 195 200 205 Gly Leu Ser AlaSer Ala Gly Leu Leu Glu Gln Met Arg His Met Glu 210 215 220 Thr Gln AlaLys Asp Leu Arg Asn Gln Leu Leu Asn Tyr Arg Ser Ala 225 230 235 240 IleSer Asn His Gly Ser Lys Ile Glu Gly Leu Glu Arg Glu Leu Thr 245 250 255Asp Leu Asn Gln Glu Phe Glu Thr Leu Gln Glu Lys Ala Gln Val Asn 260 265270 Ser Arg Lys Ala Gln Thr Leu Asn Asn Asn Val Asn Arg Ala Thr Gln 275280 285 Ser Ala Lys Glu Leu Asp Val Lys Ile Lys Asn Val Ile Arg Asn Val290 295 300 His Ile Leu Leu Lys Gln Ile Ser Gly Thr Asp Gly Glu Gly AsnAsn 305 310 315 320 Val Pro Ser Gly Asp Phe Ser Arg Glu Trp Ala Glu AlaGln Arg Met 325 330 335 Met Arg Glu Leu Arg Asn Arg Asn Phe Gly Lys HisLeu Arg Glu Ala 340 345 350 Glu Ala Asp Lys Arg Glu Ser Gln Leu Leu LeuAsn Arg Ile Arg Thr 355 360 365 Trp Gln Lys Thr His Gln Gly Glu Asn AsnGly Leu Ala Asn Ser Ile 370 375 380 Arg Asp Ser Leu Asn Glu Tyr Glu AlaLys Leu Ser Asp Leu Arg Ala 385 390 395 400 Arg Leu Gln Glu Ala Ala AlaGln Ala Lys Gln Ala Asn Gly Leu Asn 405 410 415 Gln Glu Asn Glu Arg AlaLeu Gly Ala Ile Gln Arg Gln Val Lys Glu 420 425 430 Ile Asn Ser Leu GlnSer Asp Phe Thr Lys Tyr Leu Thr Thr Ala Asp 435 440 445 Ser Ser Leu LeuGln Thr Asn Ile Ala Leu Gln Leu Met Glu Lys Ser 450 455 460 Gln Lys GluTyr Glu Lys Leu Ala Ala Ser Leu Asn Glu Ala Arg Gln 465 470 475 480 GluLeu Ser Asp Lys Val Arg Glu Leu Ser Arg Ser Ala Gly Lys Thr 485 490 495Ser Leu Val Glu Glu Ala Glu Lys His Ala Arg Ser Leu Gln Glu Leu 500 505510 Ala Lys Gln Leu Glu Glu Ile Lys Arg Asn Ala Ser Gly Asp Glu Leu 515520 525 Val Arg Cys Ala Val Asp Ala Ala Thr Ala Tyr Glu Asn Ile Leu Asn530 535 540 Ala Ile Lys Ala Ala Glu Asp Ala Ala Asn Arg Ala Ala Ser AlaSer 545 550 555 560 Glu Ser Ala Leu Gln Thr Val Ile Lys Glu Asp Leu ProArg Lys Ala 565 570 575 Lys Thr Leu Ser Ser Asn Ser Asp Lys Leu Leu AsnGlu Ala Lys Met 580 585 590 Thr Gln Lys Lys Leu Lys Gln Glu Val Ser ProAla Leu Asn Asn Leu 595 600 605 Gln Gln Thr Leu Asn Ile Val Thr Val GlnLys Glu Val Ile Asp Thr 610 615 620 Asn Leu Thr Thr Leu Arg Asp Gly LeuHis Gly Ile Gln Arg Gly Asp 625 630 635 640 Ile Asp Ala Met Ile Ser SerAla Lys Ser Met Val Arg Lys Ala Asn 645 650 655 Asp Ile Thr Asp Glu ValLeu Asp Gly Leu Asn Pro Ile Gln Thr Asp 660 665 670 Val Glu Arg Ile LysAsp Thr Tyr Gly Arg Thr Gln Asn Glu Asp Phe 675 680 685 Lys Lys Ala LeuThr Asp Ala Asp Asn Ser Val Asn Lys Leu Thr Asn 690 695 700 Lys Leu ProAsp Leu Trp Arg Lys Ile Glu Ser Ile Asn Gln Gln Leu 705 710 715 720 LeuPro Leu Gly Asn Ile Ser Asp Asn Met Asp Arg Ile Arg Glu Leu 725 730 735Ile Gln Gln Ala Arg Asp Ala Ala Ser Lys Val Ala Val Pro Met Arg 740 745750 Phe Asn Gly Lys Ser Gly Val Glu Val Arg Leu Pro Asn Asp Leu Glu 755760 765 Asp Leu Lys Gly Tyr Thr Ser Leu Ser Leu Phe Leu Gln Arg Pro Asn770 775 780 Ser Arg Glu Asn Gly Gly Thr Glu Asn Met Phe Val Met Tyr LeuGly 785 790 795 800 Asn Lys Asp Ala Ser Arg Asp Tyr Ile Gly Met Ala ValVal Asp Gly 805 810 815 Gln Leu Thr Cys Val Tyr Asn Leu Gly Asp Arg GluAla Glu Leu Gln 820 825 830 Val Asp Gln Ile Leu Thr Lys Ser Glu Thr LysGlu Ala Val Met Asp 835 840 845 Arg Val Lys Phe Gln Arg Ile Tyr Gln PheAla Arg Leu Asn Tyr Thr 850 855 860 Lys Gly Ala Thr Ser Ser Lys Pro GluThr Pro Gly Val Tyr Asp Met 865 870 875 880 Asp Gly Arg Asn Ser Asn ThrLeu Leu Asn Leu Asp Pro Glu Asn Val 885 890 895 Val Phe Tyr Val Gly GlyTyr Pro Pro Asp Phe Lys Leu Pro Ser Arg 900 905 910 Leu Ser Phe Pro ProTyr Lys Gly Cys Ile Glu Leu Asp Asp Leu Asn 915 920 925 Glu Asn Val LeuSer Leu Tyr Asn Phe Lys Lys Thr Phe Asn Leu Asn 930 935 940 Thr Thr GluVal Glu Pro Cys Arg Arg Arg Lys Glu Glu Ser Asp Lys 945 950 955 960 AsnTyr Phe Glu Gly Thr Gly Tyr Ala Arg Val Pro Thr Gln Pro His 965 970 975Ala Pro Ile Pro Thr Phe Gly Gln Thr Ile Gln Thr Thr Val Asp Arg 980 985990 Gly Leu Leu Phe Phe Ala Glu Asn Gly Asp Arg Phe Ile Ser Leu Asn 9951000 1005 Ile Glu Asp Gly Lys Leu Met Val Arg Tyr Lys Leu Asn Ser GluLeu 1010 1015 1020 Pro Lys Glu Arg Gly Val Gly Asp Ala Ile Asn Asn GlyArg Asp His 1025 1030 1035 1040 Ser Ile Gln Ile Lys Ile Gly Lys Leu GlnLys Arg Met Trp Ile Asn 1045 1050 1055 Val Asp Val Gln Asn Thr Ile IleAsp Gly Glu Val Phe Asp Phe Ser 1060 1065 1070 Thr Tyr Tyr Leu Gly GlyIle Pro Ile Ala Ile Arg Glu Arg Phe Asn 1075 1080 1085 Ile Ser Thr ProAla Phe Arg Gly Cys Met Lys Asn Leu Lys Lys Thr 1090 1095 1100 Ser GlyVal Val Arg Leu Asn Asp Thr Val Gly Val Thr Lys Lys Cys 1105 1110 11151120 Ser Glu Asp Trp Lys Leu Val Arg Ser Ala Ser Phe Ser Arg Gly Gly1125 1130 1135 Gln Leu Ser Phe Thr Asp Leu Gly Leu Pro Pro Thr Asp HisLeu Gln 1140 1145 1150 Ala Ser Phe Gly Phe Gln Thr Phe Gln Pro Ser GlyIle Leu Leu Asp 1155 1160 1165 His Gln Thr Trp Thr Arg Asn Leu Gln ValThr Leu Glu Asp Gly Tyr 1170 1175 1180 Ile Glu Leu Ser Thr Ser Asp SerGly Gly Pro Ile Phe Lys Ser Pro 1185 1190 1195 1200 Gln Thr Tyr Met AspGly Leu Leu His Tyr Val Ser Val Ile Ser Asp 1205 1210 1215 Asn Ser GlyLeu Arg Leu Leu Ile Asp Asp Gln Leu Leu Arg Asn Ser 1220 1225 1230 LysArg Leu Lys His Ile Ser Ser Ser Arg Gln Ser Leu Arg Leu Gly 1235 12401245 Gly Ser Asn Phe Glu Gly Cys Ile Ser Asn Val Phe Val Gln Arg Leu1250 1255 1260 Ser Leu Ser Pro Glu Val Leu Asp Leu Thr Ser Asn Ser LeuLys Arg 1265 1270 1275 1280 Asp Val Ser Leu Gly Gly Cys Ser Leu Asn LysPro Pro Phe Leu Met 1285 1290 1295 Leu Leu Lys Gly Ser Thr Arg Phe AsnLys Thr Lys Thr Phe Arg Ile 1300 1305 1310 Asn Gln Leu Leu Gln Asp ThrPro Val Ala Ser Pro Arg Ser Val Lys 1315 1320 1325 Val Trp Gln Asp AlaCys Ser Pro Leu Pro Lys Thr Gln Ala Asn His 1330 1335 1340 Gly Ala LeuGln Phe Gly Asp Ile Pro Thr Ser His Leu Leu Phe Lys 1345 1350 1355 1360Leu Pro Gln Glu Leu Leu Lys Pro Arg Ser Gln Phe Ala Val Asp Met 13651370 1375 Gln Thr Thr Ser Ser Arg Gly Leu Val Phe His Thr Gly Thr LysAsn 1380 1385 1390 Ser Phe Met Ala Leu Tyr Leu Ser Lys Gly Arg Leu ValPhe Ala Leu 1395 1400 1405 Gly Thr Asp Gly Lys Lys Leu Arg Ile Lys SerLys Glu Lys Cys Asn 1410 1415 1420 Asp Gly Lys Trp His Thr Val Val PheGly His Asp Gly Glu Lys Gly 1425 1430 1435 1440 Arg Leu Val Val Asp GlyLeu Arg Ala Arg Glu Gly Ser Leu Pro Gly 1445 1450 1455 Asn Ser Thr IleSer Ile Arg Ala Pro Val Tyr Leu Gly Ser Pro Pro 1460 1465 1470 Ser GlyLys Pro Lys Ser Leu Pro Thr Asn Ser Phe Val Gly Cys Leu 1475 1480 1485Lys Asn Phe Gln Leu Asp Ser Lys Pro Leu Tyr Thr Pro Ser Ser Ser 14901495 1500 Phe Gly Val Ser Ser Cys Leu Gly Gly Pro Leu Glu Lys Gly IleTyr 1505 1510 1515 1520 Phe Ser Glu Glu Gly Gly His Val Val Leu Ala HisSer Val Leu Leu 1525 1530 1535 Gly Pro Glu Phe Lys Leu Val Phe Ser IleArg Pro Arg Ser Leu Thr 1540 1545 1550 Gly Ile Leu Ile His Ile Gly SerGln Pro Gly Lys His Leu Cys Val 1555 1560 1565 Tyr Leu Glu Ala Gly LysVal Thr Ala Ser Met Asp Ser Gly Ala Gly 1570 1575 1580 Gly Thr Ser ThrSer Val Thr Pro Lys Gln Ser Leu Cys Asp Gly Gln 1585 1590 1595 1600 TrpHis Ser Val Ala Val Thr Ile Lys Gln His Ile Leu His Leu Glu 1605 16101615 Leu Asp Thr Asp Ser Ser Tyr Thr Ala Gly Gln Ile Pro Phe Pro Pro1620 1625 1630 Ala Ser Thr Gln Glu Pro Leu His Leu Gly Gly Ala Pro AlaAsn Leu 1635 1640 1645 Thr Thr Leu Arg Ile Pro Val Trp Lys Ser Phe PheGly Cys Leu Arg 1650 1655 1660 Asn Ile His Val Asn His Ile Pro Val ProVal Thr Glu Ala Leu Glu 1665 1670 1675 1680 Val Gln Gly Pro Val Ser LeuAsn Gly Cys Pro Asp Gln 1685 1690 9 5264 DNA Rattus norvegicus CDS(59)..(5233) sig_peptide (59)..(151) 9 gtataagagg aagaacacaa aggtttgcagcagccaggca gaacaccaag ggatcaag 58 atg ccg cct aca gtg agg tgg tca gcctgg tgc aca gga tgg ctg tgg 106 Met Pro Pro Thr Val Arg Trp Ser Ala TrpCys Thr Gly Trp Leu Trp 1 5 10 15 atc ttt ggg gca gct ctg ggc cag tgcctg ggg tat ggc tca gag cag 154 Ile Phe Gly Ala Ala Leu Gly Gln Cys LeuGly Tyr Gly Ser Glu Gln 20 25 30 caa agg gta gca ttt ctt cag cat cca gggcaa aac cat ctg caa gca 202 Gln Arg Val Ala Phe Leu Gln His Pro Gly GlnAsn His Leu Gln Ala 35 40 45 agt tat atg gag ctt aga ccc agc cag ggc tgtcgc cca gga tac tat 250 Ser Tyr Met Glu Leu Arg Pro Ser Gln Gly Cys ArgPro Gly Tyr Tyr 50 55 60 cga gac atc aaa agc ttc cct gcg gga agg tct gttccc tgc aat tgc 298 Arg Asp Ile Lys Ser Phe Pro Ala Gly Arg Ser Val ProCys Asn Cys 65 70 75 80 aac gga cat tca aat aga tgc caa gac ggc tcg ggagtg tgc att aac 346 Asn Gly His Ser Asn Arg Cys Gln Asp Gly Ser Gly ValCys Ile Asn 85 90 95 tgt cag cac aac aca gct ggg gag cac tgt gag cgt tgcaag agg ggt 394 Cys Gln His Asn Thr Ala Gly Glu His Cys Glu Arg Cys LysArg Gly 100 105 110 tac tat gga agc gcc atc cat gga tcc tgc agg gtt tgcccc tgt cct 442 Tyr Tyr Gly Ser Ala Ile His Gly Ser Cys Arg Val Cys ProCys Pro 115 120 125 cac acc aac agc ttt gcc act ggc tgt gct gtg gat ggagga gct gtg 490 His Thr Asn Ser Phe Ala Thr Gly Cys Ala Val Asp Gly GlyAla Val 130 135 140 agg tgt gcc tgc aaa ccc gga tac aca gga gca cag tgtgag agg tgt 538 Arg Cys Ala Cys Lys Pro Gly Tyr Thr Gly Ala Gln Cys GluArg Cys 145 150 155 160 gca cca gga tat ttt ggg aac ccc cag aaa ttt ggaggt agc tgc caa 586 Ala Pro Gly Tyr Phe Gly Asn Pro Gln Lys Phe Gly GlySer Cys Gln 165 170 175 cca tgc aat tgc aac agt aat ggc cag ttt ggc acttgt gat ccc cta 634 Pro Cys Asn Cys Asn Ser Asn Gly Gln Phe Gly Thr CysAsp Pro Leu 180 185 190 act gga gac tgt gta agc caa gaa ccc aaa gat ggcagc cct gca gaa 682 Thr Gly Asp Cys Val Ser Gln Glu Pro Lys Asp Gly SerPro Ala Glu 195 200 205 gaa tgt gat gac tgt gac agc tgt gtg atg act ctccta aat gac ttg 730 Glu Cys Asp Asp Cys Asp Ser Cys Val Met Thr Leu LeuAsn Asp Leu 210 215 220 gtc ccc atg ggt gag gaa ctc gcc ctg gtg aaa tcaaaa ctt cag ggg 778 Val Pro Met Gly Glu Glu Leu Ala Leu Val Lys Ser LysLeu Gln Gly 225 230 235 240 ctg agt gtg aac act ggt tct ctg gaa cag atccgg cat gtg gag atg 826 Leu Ser Val Asn Thr Gly Ser Leu Glu Gln Ile ArgHis Val Glu Met 245 250 255 cag gcc aag gac ctg agg aac cag ctg ctt ggcttc cgt tcc gcc atc 874 Gln Ala Lys Asp Leu Arg Asn Gln Leu Leu Gly PheArg Ser Ala Ile 260 265 270 tcc agt cac ggg tcc caa atg gac ggc ctg gaaaaa gaa ctc agt cat 922 Ser Ser His Gly Ser Gln Met Asp Gly Leu Glu LysGlu Leu Ser His 275 280 285 ttg tac cag gaa ttc gaa act ttg caa gaa aaggcg cag gtc aat tcc 970 Leu Tyr Gln Glu Phe Glu Thr Leu Gln Glu Lys AlaGln Val Asn Ser 290 295 300 aga aaa gca caa aca tta tat aac aac atc gatacg aca atc caa aac 1018 Arg Lys Ala Gln Thr Leu Tyr Asn Asn Ile Asp ThrThr Ile Gln Asn 305 310 315 320 gcc aaa gag ttg gac atg aag att aaa aacata ctt acg aat gtg cac 1066 Ala Lys Glu Leu Asp Met Lys Ile Lys Asn IleLeu Thr Asn Val His 325 330 335 att ctc ctg aag cag atc gct cgg cca ggtgga gaa gga atg gac ttg 1114 Ile Leu Leu Lys Gln Ile Ala Arg Pro Gly GlyGlu Gly Met Asp Leu 340 345 350 ccg gtg ggc gac tgg tcc agg gag tcg gcggaa gct cag cgc atg ttg 1162 Pro Val Gly Asp Trp Ser Arg Glu Ser Ala GluAla Gln Arg Met Leu 355 360 365 cgg gag ctg cga ggc cga gac ttt aaa aagcac ctc caa gaa gca gag 1210 Arg Glu Leu Arg Gly Arg Asp Phe Lys Lys HisLeu Gln Glu Ala Glu 370 375 380 gcc cag aaa atg gaa gcc cag ctc tta ctgaac cga atc agg acc tgg 1258 Ala Gln Lys Met Glu Ala Gln Leu Leu Leu AsnArg Ile Arg Thr Trp 385 390 395 400 ctg gaa tcc cac cag gtg gag aac aatgga ctg cta aag aat att cgg 1306 Leu Glu Ser His Gln Val Glu Asn Asn GlyLeu Leu Lys Asn Ile Arg 405 410 415 gat tca tta aat gat tat gaa gcc aaactt cag gac ctg cgt tcc gtg 1354 Asp Ser Leu Asn Asp Tyr Glu Ala Lys LeuGln Asp Leu Arg Ser Val 420 425 430 ctt cag gag gcg gca gcc cag gga aagcag gct aca ggc ctc aac cac 1402 Leu Gln Glu Ala Ala Ala Gln Gly Lys GlnAla Thr Gly Leu Asn His 435 440 445 gaa aat gag ggg gtc cta gga gcc atccag aga caa atg aag gaa atg 1450 Glu Asn Glu Gly Val Leu Gly Ala Ile GlnArg Gln Met Lys Glu Met 450 455 460 gat tcc ctg aag aag tac ctc acc gagcac ctg gcc aca gca gac gct 1498 Asp Ser Leu Lys Lys Tyr Leu Thr Glu HisLeu Ala Thr Ala Asp Ala 465 470 475 480 tcc ctg ctg caa acc aac agt ctactg cag cgg atg gac acg agc cag 1546 Ser Leu Leu Gln Thr Asn Ser Leu LeuGln Arg Met Asp Thr Ser Gln 485 490 495 aag gag tat gaa agc tta gct gctgct tta aac gga gca aga cag gaa 1594 Lys Glu Tyr Glu Ser Leu Ala Ala AlaLeu Asn Gly Ala Arg Gln Glu 500 505 510 ctg aat gac caa gtg cgg gaa ctctcc aga tcc gga ggc aaa gca ccc 1642 Leu Asn Asp Gln Val Arg Glu Leu SerArg Ser Gly Gly Lys Ala Pro 515 520 525 ctg gtg gct gag gcc gag aag cacgct cag tct tta cag gag ctg gca 1690 Leu Val Ala Glu Ala Glu Lys His AlaGln Ser Leu Gln Glu Leu Ala 530 535 540 aag cag ctg gaa gag ata aag agaaac acc agt ggg gat gag tcg gtg 1738 Lys Gln Leu Glu Glu Ile Lys Arg AsnThr Ser Gly Asp Glu Ser Val 545 550 555 560 cgc tgt gtc gtg gac gct gccact gcc tat gag agc atc ctc aac gcc 1786 Arg Cys Val Val Asp Ala Ala ThrAla Tyr Glu Ser Ile Leu Asn Ala 565 570 575 atc cga gca gca gag gat gcagcc ggc aag gcc gac agt gcc tca gag 1834 Ile Arg Ala Ala Glu Asp Ala AlaGly Lys Ala Asp Ser Ala Ser Glu 580 585 590 tcc gcc ttc cag aca gtg ataaag gaa gat ctt ccg aga aga gcc aaa 1882 Ser Ala Phe Gln Thr Val Ile LysGlu Asp Leu Pro Arg Arg Ala Lys 595 600 605 acc ctg agt tct gac agc gaggaa ctg tta aac gag gcc aag atg aca 1930 Thr Leu Ser Ser Asp Ser Glu GluLeu Leu Asn Glu Ala Lys Met Thr 610 615 620 cgg aaa agg cta cag caa gaaatc aat cca gct ctc aac agc cta cag 1978 Arg Lys Arg Leu Gln Gln Glu IleAsn Pro Ala Leu Asn Ser Leu Gln 625 630 635 640 caa acc ctg aag act gtatca gtt cag aag gac ctg cta gat gcc aat 2026 Gln Thr Leu Lys Thr Val SerVal Gln Lys Asp Leu Leu Asp Ala Asn 645 650 655 gtc act gct gtc cgt aatgac ctt cgt ggg atc cag aga ggt gat att 2074 Val Thr Ala Val Arg Asn AspLeu Arg Gly Ile Gln Arg Gly Asp Ile 660 665 670 gac agt gtg gtg agt ggagcg aag agc atg gtc agg aaa gcc aat ggg 2122 Asp Ser Val Val Ser Gly AlaLys Ser Met Val Arg Lys Ala Asn Gly 675 680 685 ata acg agc gag gtc ctggac ggg ctc agc ccc atc cag acg gat ttg 2170 Ile Thr Ser Glu Val Leu AspGly Leu Ser Pro Ile Gln Thr Asp Leu 690 695 700 gga agg att aag gac agctac ggg agc aca cgg cat gag gac ttc aac 2218 Gly Arg Ile Lys Asp Ser TyrGly Ser Thr Arg His Glu Asp Phe Asn 705 710 715 720 aaa gct ctg att gacgcc aat aac tca gta aag aaa tta acc aag aag 2266 Lys Ala Leu Ile Asp AlaAsn Asn Ser Val Lys Lys Leu Thr Lys Lys 725 730 735 ttg cct gat ctt tttgtc aag att gaa agc atc aat caa cag ttg ctg 2314 Leu Pro Asp Leu Phe ValLys Ile Glu Ser Ile Asn Gln Gln Leu Leu 740 745 750 ccc ctg gga aac atctct gac aat gta gac cga atc cga gag ctc att 2362 Pro Leu Gly Asn Ile SerAsp Asn Val Asp Arg Ile Arg Glu Leu Ile 755 760 765 acg cag gcc aga gatgct gcg aac aag gtt gca att ccc atg agg ttc 2410 Thr Gln Ala Arg Asp AlaAla Asn Lys Val Ala Ile Pro Met Arg Phe 770 775 780 aat ggt aaa tct ggtgtt gaa gtc cgt ctg cca aat gac cta gaa gac 2458 Asn Gly Lys Ser Gly ValGlu Val Arg Leu Pro Asn Asp Leu Glu Asp 785 790 795 800 ttg aag gga tacacg tct ctg tct ttg ttc ctc caa aga cca gac tta 2506 Leu Lys Gly Tyr ThrSer Leu Ser Leu Phe Leu Gln Arg Pro Asp Leu 805 810 815 aga gag aat ggaggc act gag gac atg ttt gta atg tac ctt gga aac 2554 Arg Glu Asn Gly GlyThr Glu Asp Met Phe Val Met Tyr Leu Gly Asn 820 825 830 aag gat gcc tccaag gac tac atc ggc atg gcg gtt gta gat ggc cag 2602 Lys Asp Ala Ser LysAsp Tyr Ile Gly Met Ala Val Val Asp Gly Gln 835 840 845 ctg acg tgt gtctac aac ctg ggg gac cga gaa gct gaa gtt cag atc 2650 Leu Thr Cys Val TyrAsn Leu Gly Asp Arg Glu Ala Glu Val Gln Ile 850 855 860 gat cag gtc ctgacg gag agt gag tct cag gag gca gtt atg gac cgg 2698 Asp Gln Val Leu ThrGlu Ser Glu Ser Gln Glu Ala Val Met Asp Arg 865 870 875 880 gtg aag ttccag aga ata tat caa ttt gcc aag ctt aat tac acc aaa 2746 Val Lys Phe GlnArg Ile Tyr Gln Phe Ala Lys Leu Asn Tyr Thr Lys 885 890 895 gaa gcc acgtcc aat aaa ccc aaa gct ccc gcg gtc tac gac ctg gag 2794 Glu Ala Thr SerAsn Lys Pro Lys Ala Pro Ala Val Tyr Asp Leu Glu 900 905 910 ggt ggc agtagc aac acg ctc ctt aat ttg gat ccc gag gac gct gtg 2842 Gly Gly Ser SerAsn Thr Leu Leu Asn Leu Asp Pro Glu Asp Ala Val 915 920 925 ttt tat gtcgga ggt tac cca ccg gat ttt gaa ctt cct agc aga ctg 2890 Phe Tyr Val GlyGly Tyr Pro Pro Asp Phe Glu Leu Pro Ser Arg Leu 930 935 940 cgg ttc cctcca tac aaa ggc tgt atc gaa cta gat gac ctc aat gaa 2938 Arg Phe Pro ProTyr Lys Gly Cys Ile Glu Leu Asp Asp Leu Asn Glu 945 950 955 960 aac gttcta agc ttg tac aat ttc aag aca act ttc aat ctc aac acc 2986 Asn Val LeuSer Leu Tyr Asn Phe Lys Thr Thr Phe Asn Leu Asn Thr 965 970 975 acg gaggtg gag cct tgt agg agg aga aag gaa gag tca gac aaa aat 3034 Thr Glu ValGlu Pro Cys Arg Arg Arg Lys Glu Glu Ser Asp Lys Asn 980 985 990 tac tttgaa ggt aca ggc tat gct cgc atc cct act caa cca aat gct 3082 Tyr Phe GluGly Thr Gly Tyr Ala Arg Ile Pro Thr Gln Pro Asn Ala 995 1000 1005 cccttc cca aac ttc ata cag acc atc cag act act gtg gac aga ggt 3130 Pro PhePro Asn Phe Ile Gln Thr Ile Gln Thr Thr Val Asp Arg Gly 1010 1015 1020tta ctg ttc ttc gca gaa aac cag gat aac ttc ata tct ctg aac ata 3178 LeuLeu Phe Phe Ala Glu Asn Gln Asp Asn Phe Ile Ser Leu Asn Ile 1025 10301035 1040 gaa gat ggc aat ctc atg gtg aga tac aaa cta aat tca gag ccaccc 3226 Glu Asp Gly Asn Leu Met Val Arg Tyr Lys Leu Asn Ser Glu Pro Pro1045 1050 1055 aaa gag aag gga att cga gac acc atc aac gat ggg aaa gatcat tcg 3274 Lys Glu Lys Gly Ile Arg Asp Thr Ile Asn Asp Gly Lys Asp HisSer 1060 1065 1070 atc tta atc aca att gga aaa cta caa aaa cgc atg tggata aat gtg 3322 Ile Leu Ile Thr Ile Gly Lys Leu Gln Lys Arg Met Trp IleAsn Val 1075 1080 1085 aac gaa cgc agt gta cga atc gaa ggg gaa ata tttgat ttc agc aca 3370 Asn Glu Arg Ser Val Arg Ile Glu Gly Glu Ile Phe AspPhe Ser Thr 1090 1095 1100 tat tat ttg ggc gga att cca att gca atc agagaa agg ttt aac atc 3418 Tyr Tyr Leu Gly Gly Ile Pro Ile Ala Ile Arg GluArg Phe Asn Ile 1105 1110 1115 1120 tca acg cct gct ttc caa ggc tgc atgaag aat ctg aag aaa acc agt 3466 Ser Thr Pro Ala Phe Gln Gly Cys Met LysAsn Leu Lys Lys Thr Ser 1125 1130 1135 ggg gtt gtc agg ttg aat gat actgtg ggt gta acc aag aag tgc tca 3514 Gly Val Val Arg Leu Asn Asp Thr ValGly Val Thr Lys Lys Cys Ser 1140 1145 1150 gaa gac tgg aag ctt gtg cgaacc gcc tcg ttc tcc aga gga ggg cag 3562 Glu Asp Trp Lys Leu Val Arg ThrAla Ser Phe Ser Arg Gly Gly Gln 1155 1160 1165 atg agc ttt aca aac ttggac gtg ccc tcg act gac cgc ttc cag ctc 3610 Met Ser Phe Thr Asn Leu AspVal Pro Ser Thr Asp Arg Phe Gln Leu 1170 1175 1180 tcc ttt ggg ttt cagacc ttt caa ccc agt ggc aca ctg ctc aat cat 3658 Ser Phe Gly Phe Gln ThrPhe Gln Pro Ser Gly Thr Leu Leu Asn His 1185 1190 1195 1200 cag acg cggaca agc agc ctg ctg gtc acc ctg gaa gat ggg cac att 3706 Gln Thr Arg ThrSer Ser Leu Leu Val Thr Leu Glu Asp Gly His Ile 1205 1210 1215 gag ttgagc act agg gac agc aac atc cca att ttc aag tct cca ggg 3754 Glu Leu SerThr Arg Asp Ser Asn Ile Pro Ile Phe Lys Ser Pro Gly 1220 1225 1230 acctac atg gac ggt tta ctg cat cat gta tct gta ata agt gac acc 3802 Thr TyrMet Asp Gly Leu Leu His His Val Ser Val Ile Ser Asp Thr 1235 1240 1245tca ggt ctc cgc ctt ctc atc gat gac cag gtc ctg aga agg aac cag 3850 SerGly Leu Arg Leu Leu Ile Asp Asp Gln Val Leu Arg Arg Asn Gln 1250 12551260 agg ctt cct agc ttc tct aac gcc cag cag tcg ctc cgc ctt gga gga3898 Arg Leu Pro Ser Phe Ser Asn Ala Gln Gln Ser Leu Arg Leu Gly Gly1265 1270 1275 1280 ggt cat ttc gag ggt tgt atc agc aat gtt tta gtc caaagg ttt tca 3946 Gly His Phe Glu Gly Cys Ile Ser Asn Val Leu Val Gln ArgPhe Ser 1285 1290 1295 cag agt cca gaa gtc ctg gat ctg gcc agt aaa tctacc aag aag gat 3994 Gln Ser Pro Glu Val Leu Asp Leu Ala Ser Lys Ser ThrLys Lys Asp 1300 1305 1310 gca tcc cta gga ggc tgc agt tta aac aag ccacct ttt ctt atg ttg 4042 Ala Ser Leu Gly Gly Cys Ser Leu Asn Lys Pro ProPhe Leu Met Leu 1315 1320 1325 ttt aaa agt ccc aag aga ttt aac aag ggccgg att ttc aat gtt aat 4090 Phe Lys Ser Pro Lys Arg Phe Asn Lys Gly ArgIle Phe Asn Val Asn 1330 1335 1340 cag ctg atg caa gat gca cct cag gccaca agg agc aca gag gct tgg 4138 Gln Leu Met Gln Asp Ala Pro Gln Ala ThrArg Ser Thr Glu Ala Trp 1345 1350 1355 1360 caa gat ggg agg tcc tgc ctacca cct ctg aac acc aag gcc tct cac 4186 Gln Asp Gly Arg Ser Cys Leu ProPro Leu Asn Thr Lys Ala Ser His 1365 1370 1375 aga gcc ctg cag ttt ggagac agc ccc acc agc cac ttg cta ctc aag 4234 Arg Ala Leu Gln Phe Gly AspSer Pro Thr Ser His Leu Leu Leu Lys 1380 1385 1390 ctt ccc cag gaa ctgctg aaa cct agg tca cag ttt tct tta gac ata 4282 Leu Pro Gln Glu Leu LeuLys Pro Arg Ser Gln Phe Ser Leu Asp Ile 1395 1400 1405 cag aca act tccccc aaa gga ctg gtg ttt tac gca ggc acc aag gac 4330 Gln Thr Thr Ser ProLys Gly Leu Val Phe Tyr Ala Gly Thr Lys Asp 1410 1415 1420 tcc ttc ctggct ctt tat gtc gca gat ggc cgt gtt gtc ttt gct ttg 4378 Ser Phe Leu AlaLeu Tyr Val Ala Asp Gly Arg Val Val Phe Ala Leu 1425 1430 1435 1440 ggggca gga ggg aag aaa ctg aga ctc agg agc aag gag aga tac cat 4426 Gly AlaGly Gly Lys Lys Leu Arg Leu Arg Ser Lys Glu Arg Tyr His 1445 1450 1455gac ggg aag tgg cac acg gtg gtg ttc gga cta aat gga gga aag gca 4474 AspGly Lys Trp His Thr Val Val Phe Gly Leu Asn Gly Gly Lys Ala 1460 14651470 cgc ctg gtt gtg gat ggg cta agg gcc cag gaa ggc agt ttg cct gga4522 Arg Leu Val Val Asp Gly Leu Arg Ala Gln Glu Gly Ser Leu Pro Gly1475 1480 1485 aat tct acc atc agc ccc aga gaa cag gtt tac cta ggg ttgccg cta 4570 Asn Ser Thr Ile Ser Pro Arg Glu Gln Val Tyr Leu Gly Leu ProLeu 1490 1495 1500 tca aga aag cca aag agc cta ccc cag cac agt ttt gtgggg tgc ctg 4618 Ser Arg Lys Pro Lys Ser Leu Pro Gln His Ser Phe Val GlyCys Leu 1505 1510 1515 1520 aga gat ttc cag ttg aac tcg aaa ccc ctg gattct cct tct gcg agg 4666 Arg Asp Phe Gln Leu Asn Ser Lys Pro Leu Asp SerPro Ser Ala Arg 1525 1530 1535 ttt ggg gta tct ccc tgc ttg ggt ggc tcttta gag aaa ggc att tat 4714 Phe Gly Val Ser Pro Cys Leu Gly Gly Ser LeuGlu Lys Gly Ile Tyr 1540 1545 1550 ttc tcc caa gga gga ggc cat gtg atccta gcc aat tct gtg tcc ttg 4762 Phe Ser Gln Gly Gly Gly His Val Ile LeuAla Asn Ser Val Ser Leu 1555 1560 1565 ggg cca gag ctt aag ctc act ttcagc att cgc cca cgg agt ctc act 4810 Gly Pro Glu Leu Lys Leu Thr Phe SerIle Arg Pro Arg Ser Leu Thr 1570 1575 1580 ggg gtc tta ata cac gtc ggaagt caa tct gga cag cgc tta agt gtg 4858 Gly Val Leu Ile His Val Gly SerGln Ser Gly Gln Arg Leu Ser Val 1585 1590 1595 1600 tac atg gag gca ggaaag gtc aca acc tct gtg agc agt gat gca gga 4906 Tyr Met Glu Ala Gly LysVal Thr Thr Ser Val Ser Ser Asp Ala Gly 1605 1610 1615 gga agt gtg acatca att aca ccg aag cag tct ctg tgt gat gga cag 4954 Gly Ser Val Thr SerIle Thr Pro Lys Gln Ser Leu Cys Asp Gly Gln 1620 1625 1630 tgg cac tcggtg gca gtc tcc att aaa cag cgc atc ctg cat cta gaa 5002 Trp His Ser ValAla Val Ser Ile Lys Gln Arg Ile Leu His Leu Glu 1635 1640 1645 ctg gataca gac agt agc tac aca gtc gca cca ctt tcc ttc tca cca 5050 Leu Asp ThrAsp Ser Ser Tyr Thr Val Ala Pro Leu Ser Phe Ser Pro 1650 1655 1660 aacagc acc cga ggg tca ctg cac gtc gga ggt gtc cca gac aaa ttg 5098 Asn SerThr Arg Gly Ser Leu His Val Gly Gly Val Pro Asp Lys Leu 1665 1670 16751680 aaa atg ctt aca ctc cct gtg tgg aac tca ttt ttt ggc tgt ctg aag5146 Lys Met Leu Thr Leu Pro Val Trp Asn Ser Phe Phe Gly Cys Leu Lys1685 1690 1695 aat att caa gtc aac cat gtc cct gtc ccc atc aca gaa gccaca gaa 5194 Asn Ile Gln Val Asn His Val Pro Val Pro Ile Thr Glu Ala ThrGlu 1700 1705 1710 gtc caa ggt tct gtc agc ctg aat ggc tgc cct gac cactaaccctaca 5243 Val Gln Gly Ser Val Ser Leu Asn Gly Cys Pro Asp His 17151720 1725 cagcaagatt cacctttgga g 5264 10 1725 PRT Rattus norvegicus 10Met Pro Pro Thr Val Arg Trp Ser Ala Trp Cys Thr Gly Trp Leu Trp 1 5 1015 Ile Phe Gly Ala Ala Leu Gly Gln Cys Leu Gly Tyr Gly Ser Glu Gln 20 2530 Gln Arg Val Ala Phe Leu Gln His Pro Gly Gln Asn His Leu Gln Ala 35 4045 Ser Tyr Met Glu Leu Arg Pro Ser Gln Gly Cys Arg Pro Gly Tyr Tyr 50 5560 Arg Asp Ile Lys Ser Phe Pro Ala Gly Arg Ser Val Pro Cys Asn Cys 65 7075 80 Asn Gly His Ser Asn Arg Cys Gln Asp Gly Ser Gly Val Cys Ile Asn 8590 95 Cys Gln His Asn Thr Ala Gly Glu His Cys Glu Arg Cys Lys Arg Gly100 105 110 Tyr Tyr Gly Ser Ala Ile His Gly Ser Cys Arg Val Cys Pro CysPro 115 120 125 His Thr Asn Ser Phe Ala Thr Gly Cys Ala Val Asp Gly GlyAla Val 130 135 140 Arg Cys Ala Cys Lys Pro Gly Tyr Thr Gly Ala Gln CysGlu Arg Cys 145 150 155 160 Ala Pro Gly Tyr Phe Gly Asn Pro Gln Lys PheGly Gly Ser Cys Gln 165 170 175 Pro Cys Asn Cys Asn Ser Asn Gly Gln PheGly Thr Cys Asp Pro Leu 180 185 190 Thr Gly Asp Cys Val Ser Gln Glu ProLys Asp Gly Ser Pro Ala Glu 195 200 205 Glu Cys Asp Asp Cys Asp Ser CysVal Met Thr Leu Leu Asn Asp Leu 210 215 220 Val Pro Met Gly Glu Glu LeuAla Leu Val Lys Ser Lys Leu Gln Gly 225 230 235 240 Leu Ser Val Asn ThrGly Ser Leu Glu Gln Ile Arg His Val Glu Met 245 250 255 Gln Ala Lys AspLeu Arg Asn Gln Leu Leu Gly Phe Arg Ser Ala Ile 260 265 270 Ser Ser HisGly Ser Gln Met Asp Gly Leu Glu Lys Glu Leu Ser His 275 280 285 Leu TyrGln Glu Phe Glu Thr Leu Gln Glu Lys Ala Gln Val Asn Ser 290 295 300 ArgLys Ala Gln Thr Leu Tyr Asn Asn Ile Asp Thr Thr Ile Gln Asn 305 310 315320 Ala Lys Glu Leu Asp Met Lys Ile Lys Asn Ile Leu Thr Asn Val His 325330 335 Ile Leu Leu Lys Gln Ile Ala Arg Pro Gly Gly Glu Gly Met Asp Leu340 345 350 Pro Val Gly Asp Trp Ser Arg Glu Ser Ala Glu Ala Gln Arg MetLeu 355 360 365 Arg Glu Leu Arg Gly Arg Asp Phe Lys Lys His Leu Gln GluAla Glu 370 375 380 Ala Gln Lys Met Glu Ala Gln Leu Leu Leu Asn Arg IleArg Thr Trp 385 390 395 400 Leu Glu Ser His Gln Val Glu Asn Asn Gly LeuLeu Lys Asn Ile Arg 405 410 415 Asp Ser Leu Asn Asp Tyr Glu Ala Lys LeuGln Asp Leu Arg Ser Val 420 425 430 Leu Gln Glu Ala Ala Ala Gln Gly LysGln Ala Thr Gly Leu Asn His 435 440 445 Glu Asn Glu Gly Val Leu Gly AlaIle Gln Arg Gln Met Lys Glu Met 450 455 460 Asp Ser Leu Lys Lys Tyr LeuThr Glu His Leu Ala Thr Ala Asp Ala 465 470 475 480 Ser Leu Leu Gln ThrAsn Ser Leu Leu Gln Arg Met Asp Thr Ser Gln 485 490 495 Lys Glu Tyr GluSer Leu Ala Ala Ala Leu Asn Gly Ala Arg Gln Glu 500 505 510 Leu Asn AspGln Val Arg Glu Leu Ser Arg Ser Gly Gly Lys Ala Pro 515 520 525 Leu ValAla Glu Ala Glu Lys His Ala Gln Ser Leu Gln Glu Leu Ala 530 535 540 LysGln Leu Glu Glu Ile Lys Arg Asn Thr Ser Gly Asp Glu Ser Val 545 550 555560 Arg Cys Val Val Asp Ala Ala Thr Ala Tyr Glu Ser Ile Leu Asn Ala 565570 575 Ile Arg Ala Ala Glu Asp Ala Ala Gly Lys Ala Asp Ser Ala Ser Glu580 585 590 Ser Ala Phe Gln Thr Val Ile Lys Glu Asp Leu Pro Arg Arg AlaLys 595 600 605 Thr Leu Ser Ser Asp Ser Glu Glu Leu Leu Asn Glu Ala LysMet Thr 610 615 620 Arg Lys Arg Leu Gln Gln Glu Ile Asn Pro Ala Leu AsnSer Leu Gln 625 630 635 640 Gln Thr Leu Lys Thr Val Ser Val Gln Lys AspLeu Leu Asp Ala Asn 645 650 655 Val Thr Ala Val Arg Asn Asp Leu Arg GlyIle Gln Arg Gly Asp Ile 660 665 670 Asp Ser Val Val Ser Gly Ala Lys SerMet Val Arg Lys Ala Asn Gly 675 680 685 Ile Thr Ser Glu Val Leu Asp GlyLeu Ser Pro Ile Gln Thr Asp Leu 690 695 700 Gly Arg Ile Lys Asp Ser TyrGly Ser Thr Arg His Glu Asp Phe Asn 705 710 715 720 Lys Ala Leu Ile AspAla Asn Asn Ser Val Lys Lys Leu Thr Lys Lys 725 730 735 Leu Pro Asp LeuPhe Val Lys Ile Glu Ser Ile Asn Gln Gln Leu Leu 740 745 750 Pro Leu GlyAsn Ile Ser Asp Asn Val Asp Arg Ile Arg Glu Leu Ile 755 760 765 Thr GlnAla Arg Asp Ala Ala Asn Lys Val Ala Ile Pro Met Arg Phe 770 775 780 AsnGly Lys Ser Gly Val Glu Val Arg Leu Pro Asn Asp Leu Glu Asp 785 790 795800 Leu Lys Gly Tyr Thr Ser Leu Ser Leu Phe Leu Gln Arg Pro Asp Leu 805810 815 Arg Glu Asn Gly Gly Thr Glu Asp Met Phe Val Met Tyr Leu Gly Asn820 825 830 Lys Asp Ala Ser Lys Asp Tyr Ile Gly Met Ala Val Val Asp GlyGln 835 840 845 Leu Thr Cys Val Tyr Asn Leu Gly Asp Arg Glu Ala Glu ValGln Ile 850 855 860 Asp Gln Val Leu Thr Glu Ser Glu Ser Gln Glu Ala ValMet Asp Arg 865 870 875 880 Val Lys Phe Gln Arg Ile Tyr Gln Phe Ala LysLeu Asn Tyr Thr Lys 885 890 895 Glu Ala Thr Ser Asn Lys Pro Lys Ala ProAla Val Tyr Asp Leu Glu 900 905 910 Gly Gly Ser Ser Asn Thr Leu Leu AsnLeu Asp Pro Glu Asp Ala Val 915 920 925 Phe Tyr Val Gly Gly Tyr Pro ProAsp Phe Glu Leu Pro Ser Arg Leu 930 935 940 Arg Phe Pro Pro Tyr Lys GlyCys Ile Glu Leu Asp Asp Leu Asn Glu 945 950 955 960 Asn Val Leu Ser LeuTyr Asn Phe Lys Thr Thr Phe Asn Leu Asn Thr 965 970 975 Thr Glu Val GluPro Cys Arg Arg Arg Lys Glu Glu Ser Asp Lys Asn 980 985 990 Tyr Phe GluGly Thr Gly Tyr Ala Arg Ile Pro Thr Gln Pro Asn Ala 995 1000 1005 ProPhe Pro Asn Phe Ile Gln Thr Ile Gln Thr Thr Val Asp Arg Gly 1010 10151020 Leu Leu Phe Phe Ala Glu Asn Gln Asp Asn Phe Ile Ser Leu Asn Ile1025 1030 1035 1040 Glu Asp Gly Asn Leu Met Val Arg Tyr Lys Leu Asn SerGlu Pro Pro 1045 1050 1055 Lys Glu Lys Gly Ile Arg Asp Thr Ile Asn AspGly Lys Asp His Ser 1060 1065 1070 Ile Leu Ile Thr Ile Gly Lys Leu GlnLys Arg Met Trp Ile Asn Val 1075 1080 1085 Asn Glu Arg Ser Val Arg IleGlu Gly Glu Ile Phe Asp Phe Ser Thr 1090 1095 1100 Tyr Tyr Leu Gly GlyIle Pro Ile Ala Ile Arg Glu Arg Phe Asn Ile 1105 1110 1115 1120 Ser ThrPro Ala Phe Gln Gly Cys Met Lys Asn Leu Lys Lys Thr Ser 1125 1130 1135Gly Val Val Arg Leu Asn Asp Thr Val Gly Val Thr Lys Lys Cys Ser 11401145 1150 Glu Asp Trp Lys Leu Val Arg Thr Ala Ser Phe Ser Arg Gly GlyGln 1155 1160 1165 Met Ser Phe Thr Asn Leu Asp Val Pro Ser Thr Asp ArgPhe Gln Leu 1170 1175 1180 Ser Phe Gly Phe Gln Thr Phe Gln Pro Ser GlyThr Leu Leu Asn His 1185 1190 1195 1200 Gln Thr Arg Thr Ser Ser Leu LeuVal Thr Leu Glu Asp Gly His Ile 1205 1210 1215 Glu Leu Ser Thr Arg AspSer Asn Ile Pro Ile Phe Lys Ser Pro Gly 1220 1225 1230 Thr Tyr Met AspGly Leu Leu His His Val Ser Val Ile Ser Asp Thr 1235 1240 1245 Ser GlyLeu Arg Leu Leu Ile Asp Asp Gln Val Leu Arg Arg Asn Gln 1250 1255 1260Arg Leu Pro Ser Phe Ser Asn Ala Gln Gln Ser Leu Arg Leu Gly Gly 12651270 1275 1280 Gly His Phe Glu Gly Cys Ile Ser Asn Val Leu Val Gln ArgPhe Ser 1285 1290 1295 Gln Ser Pro Glu Val Leu Asp Leu Ala Ser Lys SerThr Lys Lys Asp 1300 1305 1310 Ala Ser Leu Gly Gly Cys Ser Leu Asn LysPro Pro Phe Leu Met Leu 1315 1320 1325 Phe Lys Ser Pro Lys Arg Phe AsnLys Gly Arg Ile Phe Asn Val Asn 1330 1335 1340 Gln Leu Met Gln Asp AlaPro Gln Ala Thr Arg Ser Thr Glu Ala Trp 1345 1350 1355 1360 Gln Asp GlyArg Ser Cys Leu Pro Pro Leu Asn Thr Lys Ala Ser His 1365 1370 1375 ArgAla Leu Gln Phe Gly Asp Ser Pro Thr Ser His Leu Leu Leu Lys 1380 13851390 Leu Pro Gln Glu Leu Leu Lys Pro Arg Ser Gln Phe Ser Leu Asp Ile1395 1400 1405 Gln Thr Thr Ser Pro Lys Gly Leu Val Phe Tyr Ala Gly ThrLys Asp 1410 1415 1420 Ser Phe Leu Ala Leu Tyr Val Ala Asp Gly Arg ValVal Phe Ala Leu 1425 1430 1435 1440 Gly Ala Gly Gly Lys Lys Leu Arg LeuArg Ser Lys Glu Arg Tyr His 1445 1450 1455 Asp Gly Lys Trp His Thr ValVal Phe Gly Leu Asn Gly Gly Lys Ala 1460 1465 1470 Arg Leu Val Val AspGly Leu Arg Ala Gln Glu Gly Ser Leu Pro Gly 1475 1480 1485 Asn Ser ThrIle Ser Pro Arg Glu Gln Val Tyr Leu Gly Leu Pro Leu 1490 1495 1500 SerArg Lys Pro Lys Ser Leu Pro Gln His Ser Phe Val Gly Cys Leu 1505 15101515 1520 Arg Asp Phe Gln Leu Asn Ser Lys Pro Leu Asp Ser Pro Ser AlaArg 1525 1530 1535 Phe Gly Val Ser Pro Cys Leu Gly Gly Ser Leu Glu LysGly Ile Tyr 1540 1545 1550 Phe Ser Gln Gly Gly Gly His Val Ile Leu AlaAsn Ser Val Ser Leu 1555 1560 1565 Gly Pro Glu Leu Lys Leu Thr Phe SerIle Arg Pro Arg Ser Leu Thr 1570 1575 1580 Gly Val Leu Ile His Val GlySer Gln Ser Gly Gln Arg Leu Ser Val 1585 1590 1595 1600 Tyr Met Glu AlaGly Lys Val Thr Thr Ser Val Ser Ser Asp Ala Gly 1605 1610 1615 Gly SerVal Thr Ser Ile Thr Pro Lys Gln Ser Leu Cys Asp Gly Gln 1620 1625 1630Trp His Ser Val Ala Val Ser Ile Lys Gln Arg Ile Leu His Leu Glu 16351640 1645 Leu Asp Thr Asp Ser Ser Tyr Thr Val Ala Pro Leu Ser Phe SerPro 1650 1655 1660 Asn Ser Thr Arg Gly Ser Leu His Val Gly Gly Val ProAsp Lys Leu 1665 1670 1675 1680 Lys Met Leu Thr Leu Pro Val Trp Asn SerPhe Phe Gly Cys Leu Lys 1685 1690 1695 Asn Ile Gln Val Asn His Val ProVal Pro Ile Thr Glu Ala Thr Glu 1700 1705 1710 Val Gln Gly Ser Val SerLeu Asn Gly Cys Pro Asp His 1715 1720 1725 11 5113 DNA Rattus norvegicusCDS (1)..(5082) 11 cag caa agg gta gca ttt ctt cag cat cca ggg caa aaccat ctg caa 48 Gln Gln Arg Val Ala Phe Leu Gln His Pro Gly Gln Asn HisLeu Gln 1 5 10 15 gca agt tat atg gag ctt aga ccc agc cag ggc tgt cgccca gga tac 96 Ala Ser Tyr Met Glu Leu Arg Pro Ser Gln Gly Cys Arg ProGly Tyr 20 25 30 tat cga gac atc aaa agc ttc cct gcg gga agg tct gtt ccctgc aat 144 Tyr Arg Asp Ile Lys Ser Phe Pro Ala Gly Arg Ser Val Pro CysAsn 35 40 45 tgc aac gga cat tca aat aga tgc caa gac ggc tcg gga gtg tgcatt 192 Cys Asn Gly His Ser Asn Arg Cys Gln Asp Gly Ser Gly Val Cys Ile50 55 60 aac tgt cag cac aac aca gct ggg gag cac tgt gag cgt tgc aag agg240 Asn Cys Gln His Asn Thr Ala Gly Glu His Cys Glu Arg Cys Lys Arg 6570 75 80 ggt tac tat gga agc gcc atc cat gga tcc tgc agg gtt tgc ccc tgt288 Gly Tyr Tyr Gly Ser Ala Ile His Gly Ser Cys Arg Val Cys Pro Cys 8590 95 cct cac acc aac agc ttt gcc act ggc tgt gct gtg gat gga gga gct336 Pro His Thr Asn Ser Phe Ala Thr Gly Cys Ala Val Asp Gly Gly Ala 100105 110 gtg agg tgt gcc tgc aaa ccc gga tac aca gga gca cag tgt gag agg384 Val Arg Cys Ala Cys Lys Pro Gly Tyr Thr Gly Ala Gln Cys Glu Arg 115120 125 tgt gca cca gga tat ttt ggg aac ccc cag aaa ttt gga ggt agc tgc432 Cys Ala Pro Gly Tyr Phe Gly Asn Pro Gln Lys Phe Gly Gly Ser Cys 130135 140 caa cca tgc aat tgc aac agt aat ggc cag ttt ggc act tgt gat ccc480 Gln Pro Cys Asn Cys Asn Ser Asn Gly Gln Phe Gly Thr Cys Asp Pro 145150 155 160 cta act gga gac tgt gta agc caa gaa ccc aaa gat ggc agc cctgca 528 Leu Thr Gly Asp Cys Val Ser Gln Glu Pro Lys Asp Gly Ser Pro Ala165 170 175 gaa gaa tgt gat gac tgt gac agc tgt gtg atg act ctc cta aatgac 576 Glu Glu Cys Asp Asp Cys Asp Ser Cys Val Met Thr Leu Leu Asn Asp180 185 190 ttg gtc ccc atg ggt gag gaa ctc gcc ctg gtg aaa tca aaa cttcag 624 Leu Val Pro Met Gly Glu Glu Leu Ala Leu Val Lys Ser Lys Leu Gln195 200 205 ggg ctg agt gtg aac act ggt tct ctg gaa cag atc cgg cat gtggag 672 Gly Leu Ser Val Asn Thr Gly Ser Leu Glu Gln Ile Arg His Val Glu210 215 220 atg cag gcc aag gac ctg agg aac cag ctg ctt ggc ttc cgt tccgcc 720 Met Gln Ala Lys Asp Leu Arg Asn Gln Leu Leu Gly Phe Arg Ser Ala225 230 235 240 atc tcc agt cac ggg tcc caa atg gac ggc ctg gaa aaa gaactc agt 768 Ile Ser Ser His Gly Ser Gln Met Asp Gly Leu Glu Lys Glu LeuSer 245 250 255 cat ttg tac cag gaa ttc gaa act ttg caa gaa aag gcg caggtc aat 816 His Leu Tyr Gln Glu Phe Glu Thr Leu Gln Glu Lys Ala Gln ValAsn 260 265 270 tcc aga aaa gca caa aca tta tat aac aac atc gat acg acaatc caa 864 Ser Arg Lys Ala Gln Thr Leu Tyr Asn Asn Ile Asp Thr Thr IleGln 275 280 285 aac gcc aaa gag ttg gac atg aag att aaa aac ata ctt acgaat gtg 912 Asn Ala Lys Glu Leu Asp Met Lys Ile Lys Asn Ile Leu Thr AsnVal 290 295 300 cac att ctc ctg aag cag atc gct cgg cca ggt gga gaa ggaatg gac 960 His Ile Leu Leu Lys Gln Ile Ala Arg Pro Gly Gly Glu Gly MetAsp 305 310 315 320 ttg ccg gtg ggc gac tgg tcc agg gag tcg gcg gaa gctcag cgc atg 1008 Leu Pro Val Gly Asp Trp Ser Arg Glu Ser Ala Glu Ala GlnArg Met 325 330 335 ttg cgg gag ctg cga ggc cga gac ttt aaa aag cac ctccaa gaa gca 1056 Leu Arg Glu Leu Arg Gly Arg Asp Phe Lys Lys His Leu GlnGlu Ala 340 345 350 gag gcc cag aaa atg gaa gcc cag ctc tta ctg aac cgaatc agg acc 1104 Glu Ala Gln Lys Met Glu Ala Gln Leu Leu Leu Asn Arg IleArg Thr 355 360 365 tgg ctg gaa tcc cac cag gtg gag aac aat gga ctg ctaaag aat att 1152 Trp Leu Glu Ser His Gln Val Glu Asn Asn Gly Leu Leu LysAsn Ile 370 375 380 cgg gat tca tta aat gat tat gaa gcc aaa ctt cag gacctg cgt tcc 1200 Arg Asp Ser Leu Asn Asp Tyr Glu Ala Lys Leu Gln Asp LeuArg Ser 385 390 395 400 gtg ctt cag gag gcg gca gcc cag gga aag cag gctaca ggc ctc aac 1248 Val Leu Gln Glu Ala Ala Ala Gln Gly Lys Gln Ala ThrGly Leu Asn 405 410 415 cac gaa aat gag ggg gtc cta gga gcc atc cag agacaa atg aag gaa 1296 His Glu Asn Glu Gly Val Leu Gly Ala Ile Gln Arg GlnMet Lys Glu 420 425 430 atg gat tcc ctg aag aag tac ctc acc gag cac ctggcc aca gca gac 1344 Met Asp Ser Leu Lys Lys Tyr Leu Thr Glu His Leu AlaThr Ala Asp 435 440 445 gct tcc ctg ctg caa acc aac agt cta ctg cag cggatg gac acg agc 1392 Ala Ser Leu Leu Gln Thr Asn Ser Leu Leu Gln Arg MetAsp Thr Ser 450 455 460 cag aag gag tat gaa agc tta gct gct gct tta aacgga gca aga cag 1440 Gln Lys Glu Tyr Glu Ser Leu Ala Ala Ala Leu Asn GlyAla Arg Gln 465 470 475 480 gaa ctg aat gac caa gtg cgg gaa ctc tcc agatcc gga ggc aaa gca 1488 Glu Leu Asn Asp Gln Val Arg Glu Leu Ser Arg SerGly Gly Lys Ala 485 490 495 ccc ctg gtg gct gag gcc gag aag cac gct cagtct tta cag gag ctg 1536 Pro Leu Val Ala Glu Ala Glu Lys His Ala Gln SerLeu Gln Glu Leu 500 505 510 gca aag cag ctg gaa gag ata aag aga aac accagt ggg gat gag tcg 1584 Ala Lys Gln Leu Glu Glu Ile Lys Arg Asn Thr SerGly Asp Glu Ser 515 520 525 gtg cgc tgt gtc gtg gac gct gcc act gcc tatgag agc atc ctc aac 1632 Val Arg Cys Val Val Asp Ala Ala Thr Ala Tyr GluSer Ile Leu Asn 530 535 540 gcc atc cga gca gca gag gat gca gcc ggc aaggcc gac agt gcc tca 1680 Ala Ile Arg Ala Ala Glu Asp Ala Ala Gly Lys AlaAsp Ser Ala Ser 545 550 555 560 gag tcc gcc ttc cag aca gtg ata aag gaagat ctt ccg aga aga gcc 1728 Glu Ser Ala Phe Gln Thr Val Ile Lys Glu AspLeu Pro Arg Arg Ala 565 570 575 aaa acc ctg agt tct gac agc gag gaa ctgtta aac gag gcc aag atg 1776 Lys Thr Leu Ser Ser Asp Ser Glu Glu Leu LeuAsn Glu Ala Lys Met 580 585 590 aca cgg aaa agg cta cag caa gaa atc aatcca gct ctc aac agc cta 1824 Thr Arg Lys Arg Leu Gln Gln Glu Ile Asn ProAla Leu Asn Ser Leu 595 600 605 cag caa acc ctg aag act gta tca gtt cagaag gac ctg cta gat gcc 1872 Gln Gln Thr Leu Lys Thr Val Ser Val Gln LysAsp Leu Leu Asp Ala 610 615 620 aat gtc act gct gtc cgt aat gac ctt cgtggg atc cag aga ggt gat 1920 Asn Val Thr Ala Val Arg Asn Asp Leu Arg GlyIle Gln Arg Gly Asp 625 630 635 640 att gac agt gtg gtg agt gga gcg aagagc atg gtc agg aaa gcc aat 1968 Ile Asp Ser Val Val Ser Gly Ala Lys SerMet Val Arg Lys Ala Asn 645 650 655 ggg ata acg agc gag gtc ctg gac gggctc agc ccc atc cag acg gat 2016 Gly Ile Thr Ser Glu Val Leu Asp Gly LeuSer Pro Ile Gln Thr Asp 660 665 670 ttg gga agg att aag gac agc tac gggagc aca cgg cat gag gac ttc 2064 Leu Gly Arg Ile Lys Asp Ser Tyr Gly SerThr Arg His Glu Asp Phe 675 680 685 aac aaa gct ctg att gac gcc aat aactca gta aag aaa tta acc aag 2112 Asn Lys Ala Leu Ile Asp Ala Asn Asn SerVal Lys Lys Leu Thr Lys 690 695 700 aag ttg cct gat ctt ttt gtc aag attgaa agc atc aat caa cag ttg 2160 Lys Leu Pro Asp Leu Phe Val Lys Ile GluSer Ile Asn Gln Gln Leu 705 710 715 720 ctg ccc ctg gga aac atc tct gacaat gta gac cga atc cga gag ctc 2208 Leu Pro Leu Gly Asn Ile Ser Asp AsnVal Asp Arg Ile Arg Glu Leu 725 730 735 att acg cag gcc aga gat gct gcgaac aag gtt gca att ccc atg agg 2256 Ile Thr Gln Ala Arg Asp Ala Ala AsnLys Val Ala Ile Pro Met Arg 740 745 750 ttc aat ggt aaa tct ggt gtt gaagtc cgt ctg cca aat gac cta gaa 2304 Phe Asn Gly Lys Ser Gly Val Glu ValArg Leu Pro Asn Asp Leu Glu 755 760 765 gac ttg aag gga tac acg tct ctgtct ttg ttc ctc caa aga cca gac 2352 Asp Leu Lys Gly Tyr Thr Ser Leu SerLeu Phe Leu Gln Arg Pro Asp 770 775 780 tta aga gag aat gga ggc act gaggac atg ttt gta atg tac ctt gga 2400 Leu Arg Glu Asn Gly Gly Thr Glu AspMet Phe Val Met Tyr Leu Gly 785 790 795 800 aac aag gat gcc tcc aag gactac atc ggc atg gcg gtt gta gat ggc 2448 Asn Lys Asp Ala Ser Lys Asp TyrIle Gly Met Ala Val Val Asp Gly 805 810 815 cag ctg acg tgt gtc tac aacctg ggg gac cga gaa gct gaa gtt cag 2496 Gln Leu Thr Cys Val Tyr Asn LeuGly Asp Arg Glu Ala Glu Val Gln 820 825 830 atc gat cag gtc ctg acg gagagt gag tct cag gag gca gtt atg gac 2544 Ile Asp Gln Val Leu Thr Glu SerGlu Ser Gln Glu Ala Val Met Asp 835 840 845 cgg gtg aag ttc cag aga atatat caa ttt gcc aag ctt aat tac acc 2592 Arg Val Lys Phe Gln Arg Ile TyrGln Phe Ala Lys Leu Asn Tyr Thr 850 855 860 aaa gaa gcc acg tcc aat aaaccc aaa gct ccc gcg gtc tac gac ctg 2640 Lys Glu Ala Thr Ser Asn Lys ProLys Ala Pro Ala Val Tyr Asp Leu 865 870 875 880 gag ggt ggc agt agc aacacg ctc ctt aat ttg gat ccc gag gac gct 2688 Glu Gly Gly Ser Ser Asn ThrLeu Leu Asn Leu Asp Pro Glu Asp Ala 885 890 895 gtg ttt tat gtc gga ggttac cca ccg gat ttt gaa ctt cct agc aga 2736 Val Phe Tyr Val Gly Gly TyrPro Pro Asp Phe Glu Leu Pro Ser Arg 900 905 910 ctg cgg ttc cct cca tacaaa ggc tgt atc gaa cta gat gac ctc aat 2784 Leu Arg Phe Pro Pro Tyr LysGly Cys Ile Glu Leu Asp Asp Leu Asn 915 920 925 gaa aac gtt cta agc ttgtac aat ttc aag aca act ttc aat ctc aac 2832 Glu Asn Val Leu Ser Leu TyrAsn Phe Lys Thr Thr Phe Asn Leu Asn 930 935 940 acc acg gag gtg gag ccttgt agg agg aga aag gaa gag tca gac aaa 2880 Thr Thr Glu Val Glu Pro CysArg Arg Arg Lys Glu Glu Ser Asp Lys 945 950 955 960 aat tac ttt gaa ggtaca ggc tat gct cgc atc cct act caa cca aat 2928 Asn Tyr Phe Glu Gly ThrGly Tyr Ala Arg Ile Pro Thr Gln Pro Asn 965 970 975 gct ccc ttc cca aacttc ata cag acc atc cag act act gtg gac aga 2976 Ala Pro Phe Pro Asn PheIle Gln Thr Ile Gln Thr Thr Val Asp Arg 980 985 990 ggt tta ctg ttc ttcgca gaa aac cag gat aac ttc ata tct ctg aac 3024 Gly Leu Leu Phe Phe AlaGlu Asn Gln Asp Asn Phe Ile Ser Leu Asn 995 1000 1005 ata gaa gat ggcaat ctc atg gtg aga tac aaa cta aat tca gag cca 3072 Ile Glu Asp Gly AsnLeu Met Val Arg Tyr Lys Leu Asn Ser Glu Pro 1010 1015 1020 ccc aaa gagaag gga att cga gac acc atc aac gat ggg aaa gat cat 3120 Pro Lys Glu LysGly Ile Arg Asp Thr Ile Asn Asp Gly Lys Asp His 1025 1030 1035 1040 tcgatc tta atc aca att gga aaa cta caa aaa cgc atg tgg ata aat 3168 Ser IleLeu Ile Thr Ile Gly Lys Leu Gln Lys Arg Met Trp Ile Asn 1045 1050 1055gtg aac gaa cgc agt gta cga atc gaa ggg gaa ata ttt gat ttc agc 3216 ValAsn Glu Arg Ser Val Arg Ile Glu Gly Glu Ile Phe Asp Phe Ser 1060 10651070 aca tat tat ttg ggc gga att cca att gca atc aga gaa agg ttt aac3264 Thr Tyr Tyr Leu Gly Gly Ile Pro Ile Ala Ile Arg Glu Arg Phe Asn1075 1080 1085 atc tca acg cct gct ttc caa ggc tgc atg aag aat ctg aagaaa acc 3312 Ile Ser Thr Pro Ala Phe Gln Gly Cys Met Lys Asn Leu Lys LysThr 1090 1095 1100 agt ggg gtt gtc agg ttg aat gat act gtg ggt gta accaag aag tgc 3360 Ser Gly Val Val Arg Leu Asn Asp Thr Val Gly Val Thr LysLys Cys 1105 1110 1115 1120 tca gaa gac tgg aag ctt gtg cga acc gcc tcgttc tcc aga gga ggg 3408 Ser Glu Asp Trp Lys Leu Val Arg Thr Ala Ser PheSer Arg Gly Gly 1125 1130 1135 cag atg agc ttt aca aac ttg gac gtg ccctcg act gac cgc ttc cag 3456 Gln Met Ser Phe Thr Asn Leu Asp Val Pro SerThr Asp Arg Phe Gln 1140 1145 1150 ctc tcc ttt ggg ttt cag acc ttt caaccc agt ggc aca ctg ctc aat 3504 Leu Ser Phe Gly Phe Gln Thr Phe Gln ProSer Gly Thr Leu Leu Asn 1155 1160 1165 cat cag acg cgg aca agc agc ctgctg gtc acc ctg gaa gat ggg cac 3552 His Gln Thr Arg Thr Ser Ser Leu LeuVal Thr Leu Glu Asp Gly His 1170 1175 1180 att gag ttg agc act agg gacagc aac atc cca att ttc aag tct cca 3600 Ile Glu Leu Ser Thr Arg Asp SerAsn Ile Pro Ile Phe Lys Ser Pro 1185 1190 1195 1200 ggg acc tac atg gacggt tta ctg cat cat gta tct gta ata agt gac 3648 Gly Thr Tyr Met Asp GlyLeu Leu His His Val Ser Val Ile Ser Asp 1205 1210 1215 acc tca ggt ctccgc ctt ctc atc gat gac cag gtc ctg aga agg aac 3696 Thr Ser Gly Leu ArgLeu Leu Ile Asp Asp Gln Val Leu Arg Arg Asn 1220 1225 1230 cag agg cttcct agc ttc tct aac gcc cag cag tcg ctc cgc ctt gga 3744 Gln Arg Leu ProSer Phe Ser Asn Ala Gln Gln Ser Leu Arg Leu Gly 1235 1240 1245 gga ggtcat ttc gag ggt tgt atc agc aat gtt tta gtc caa agg ttt 3792 Gly Gly HisPhe Glu Gly Cys Ile Ser Asn Val Leu Val Gln Arg Phe 1250 1255 1260 tcacag agt cca gaa gtc ctg gat ctg gcc agt aaa tct acc aag aag 3840 Ser GlnSer Pro Glu Val Leu Asp Leu Ala Ser Lys Ser Thr Lys Lys 1265 1270 12751280 gat gca tcc cta gga ggc tgc agt tta aac aag cca cct ttt ctt atg3888 Asp Ala Ser Leu Gly Gly Cys Ser Leu Asn Lys Pro Pro Phe Leu Met1285 1290 1295 ttg ttt aaa agt ccc aag aga ttt aac aag ggc cgg att ttcaat gtt 3936 Leu Phe Lys Ser Pro Lys Arg Phe Asn Lys Gly Arg Ile Phe AsnVal 1300 1305 1310 aat cag ctg atg caa gat gca cct cag gcc aca agg agcaca gag gct 3984 Asn Gln Leu Met Gln Asp Ala Pro Gln Ala Thr Arg Ser ThrGlu Ala 1315 1320 1325 tgg caa gat ggg agg tcc tgc cta cca cct ctg aacacc aag gcc tct 4032 Trp Gln Asp Gly Arg Ser Cys Leu Pro Pro Leu Asn ThrLys Ala Ser 1330 1335 1340 cac aga gcc ctg cag ttt gga gac agc ccc accagc cac ttg cta ctc 4080 His Arg Ala Leu Gln Phe Gly Asp Ser Pro Thr SerHis Leu Leu Leu 1345 1350 1355 1360 aag ctt ccc cag gaa ctg ctg aaa cctagg tca cag ttt tct tta gac 4128 Lys Leu Pro Gln Glu Leu Leu Lys Pro ArgSer Gln Phe Ser Leu Asp 1365 1370 1375 ata cag aca act tcc ccc aaa ggactg gtg ttt tac gca ggc acc aag 4176 Ile Gln Thr Thr Ser Pro Lys Gly LeuVal Phe Tyr Ala Gly Thr Lys 1380 1385 1390 gac tcc ttc ctg gct ctt tatgtc gca gat ggc cgt gtt gtc ttt gct 4224 Asp Ser Phe Leu Ala Leu Tyr ValAla Asp Gly Arg Val Val Phe Ala 1395 1400 1405 ttg ggg gca gga ggg aagaaa ctg aga ctc agg agc aag gag aga tac 4272 Leu Gly Ala Gly Gly Lys LysLeu Arg Leu Arg Ser Lys Glu Arg Tyr 1410 1415 1420 cat gac ggg aag tggcac acg gtg gtg ttc gga cta aat gga gga aag 4320 His Asp Gly Lys Trp HisThr Val Val Phe Gly Leu Asn Gly Gly Lys 1425 1430 1435 1440 gca cgc ctggtt gtg gat ggg cta agg gcc cag gaa ggc agt ttg cct 4368 Ala Arg Leu ValVal Asp Gly Leu Arg Ala Gln Glu Gly Ser Leu Pro 1445 1450 1455 gga aattct acc atc agc ccc aga gaa cag gtt tac cta ggg ttg ccg 4416 Gly Asn SerThr Ile Ser Pro Arg Glu Gln Val Tyr Leu Gly Leu Pro 1460 1465 1470 ctatca aga aag cca aag agc cta ccc cag cac agt ttt gtg ggg tgc 4464 Leu SerArg Lys Pro Lys Ser Leu Pro Gln His Ser Phe Val Gly Cys 1475 1480 1485ctg aga gat ttc cag ttg aac tcg aaa ccc ctg gat tct cct tct gcg 4512 LeuArg Asp Phe Gln Leu Asn Ser Lys Pro Leu Asp Ser Pro Ser Ala 1490 14951500 agg ttt ggg gta tct ccc tgc ttg ggt ggc tct tta gag aaa ggc att4560 Arg Phe Gly Val Ser Pro Cys Leu Gly Gly Ser Leu Glu Lys Gly Ile1505 1510 1515 1520 tat ttc tcc caa gga gga ggc cat gtg atc cta gcc aattct gtg tcc 4608 Tyr Phe Ser Gln Gly Gly Gly His Val Ile Leu Ala Asn SerVal Ser 1525 1530 1535 ttg ggg cca gag ctt aag ctc act ttc agc att cgccca cgg agt ctc 4656 Leu Gly Pro Glu Leu Lys Leu Thr Phe Ser Ile Arg ProArg Ser Leu 1540 1545 1550 act ggg gtc tta ata cac gtc gga agt caa tctgga cag cgc tta agt 4704 Thr Gly Val Leu Ile His Val Gly Ser Gln Ser GlyGln Arg Leu Ser 1555 1560 1565 gtg tac atg gag gca gga aag gtc aca acctct gtg agc agt gat gca 4752 Val Tyr Met Glu Ala Gly Lys Val Thr Thr SerVal Ser Ser Asp Ala 1570 1575 1580 gga gga agt gtg aca tca att aca ccgaag cag tct ctg tgt gat gga 4800 Gly Gly Ser Val Thr Ser Ile Thr Pro LysGln Ser Leu Cys Asp Gly 1585 1590 1595 1600 cag tgg cac tcg gtg gca gtctcc att aaa cag cgc atc ctg cat cta 4848 Gln Trp His Ser Val Ala Val SerIle Lys Gln Arg Ile Leu His Leu 1605 1610 1615 gaa ctg gat aca gac agtagc tac aca gtc gca cca ctt tcc ttc tca 4896 Glu Leu Asp Thr Asp Ser SerTyr Thr Val Ala Pro Leu Ser Phe Ser 1620 1625 1630 cca aac agc acc cgaggg tca ctg cac gtc gga ggt gtc cca gac aaa 4944 Pro Asn Ser Thr Arg GlySer Leu His Val Gly Gly Val Pro Asp Lys 1635 1640 1645 ttg aaa atg cttaca ctc cct gtg tgg aac tca ttt ttt ggc tgt ctg 4992 Leu Lys Met Leu ThrLeu Pro Val Trp Asn Ser Phe Phe Gly Cys Leu 1650 1655 1660 aag aat attcaa gtc aac cat gtc cct gtc ccc atc aca gaa gcc aca 5040 Lys Asn Ile GlnVal Asn His Val Pro Val Pro Ile Thr Glu Ala Thr 1665 1670 1675 1680 gaagtc caa ggt tct gtc agc ctg aat ggc tgc cct gac cac 5082 Glu Val Gln GlySer Val Ser Leu Asn Gly Cys Pro Asp His 1685 1690 taaccctaca cagcaagattcacctttgga g 5113 12 1694 PRT Rattus norvegicus 12 Gln Gln Arg Val AlaPhe Leu Gln His Pro Gly Gln Asn His Leu Gln 1 5 10 15 Ala Ser Tyr MetGlu Leu Arg Pro Ser Gln Gly Cys Arg Pro Gly Tyr 20 25 30 Tyr Arg Asp IleLys Ser Phe Pro Ala Gly Arg Ser Val Pro Cys Asn 35 40 45 Cys Asn Gly HisSer Asn Arg Cys Gln Asp Gly Ser Gly Val Cys Ile 50 55 60 Asn Cys Gln HisAsn Thr Ala Gly Glu His Cys Glu Arg Cys Lys Arg 65 70 75 80 Gly Tyr TyrGly Ser Ala Ile His Gly Ser Cys Arg Val Cys Pro Cys 85 90 95 Pro His ThrAsn Ser Phe Ala Thr Gly Cys Ala Val Asp Gly Gly Ala 100 105 110 Val ArgCys Ala Cys Lys Pro Gly Tyr Thr Gly Ala Gln Cys Glu Arg 115 120 125 CysAla Pro Gly Tyr Phe Gly Asn Pro Gln Lys Phe Gly Gly Ser Cys 130 135 140Gln Pro Cys Asn Cys Asn Ser Asn Gly Gln Phe Gly Thr Cys Asp Pro 145 150155 160 Leu Thr Gly Asp Cys Val Ser Gln Glu Pro Lys Asp Gly Ser Pro Ala165 170 175 Glu Glu Cys Asp Asp Cys Asp Ser Cys Val Met Thr Leu Leu AsnAsp 180 185 190 Leu Val Pro Met Gly Glu Glu Leu Ala Leu Val Lys Ser LysLeu Gln 195 200 205 Gly Leu Ser Val Asn Thr Gly Ser Leu Glu Gln Ile ArgHis Val Glu 210 215 220 Met Gln Ala Lys Asp Leu Arg Asn Gln Leu Leu GlyPhe Arg Ser Ala 225 230 235 240 Ile Ser Ser His Gly Ser Gln Met Asp GlyLeu Glu Lys Glu Leu Ser 245 250 255 His Leu Tyr Gln Glu Phe Glu Thr LeuGln Glu Lys Ala Gln Val Asn 260 265 270 Ser Arg Lys Ala Gln Thr Leu TyrAsn Asn Ile Asp Thr Thr Ile Gln 275 280 285 Asn Ala Lys Glu Leu Asp MetLys Ile Lys Asn Ile Leu Thr Asn Val 290 295 300 His Ile Leu Leu Lys GlnIle Ala Arg Pro Gly Gly Glu Gly Met Asp 305 310 315 320 Leu Pro Val GlyAsp Trp Ser Arg Glu Ser Ala Glu Ala Gln Arg Met 325 330 335 Leu Arg GluLeu Arg Gly Arg Asp Phe Lys Lys His Leu Gln Glu Ala 340 345 350 Glu AlaGln Lys Met Glu Ala Gln Leu Leu Leu Asn Arg Ile Arg Thr 355 360 365 TrpLeu Glu Ser His Gln Val Glu Asn Asn Gly Leu Leu Lys Asn Ile 370 375 380Arg Asp Ser Leu Asn Asp Tyr Glu Ala Lys Leu Gln Asp Leu Arg Ser 385 390395 400 Val Leu Gln Glu Ala Ala Ala Gln Gly Lys Gln Ala Thr Gly Leu Asn405 410 415 His Glu Asn Glu Gly Val Leu Gly Ala Ile Gln Arg Gln Met LysGlu 420 425 430 Met Asp Ser Leu Lys Lys Tyr Leu Thr Glu His Leu Ala ThrAla Asp 435 440 445 Ala Ser Leu Leu Gln Thr Asn Ser Leu Leu Gln Arg MetAsp Thr Ser 450 455 460 Gln Lys Glu Tyr Glu Ser Leu Ala Ala Ala Leu AsnGly Ala Arg Gln 465 470 475 480 Glu Leu Asn Asp Gln Val Arg Glu Leu SerArg Ser Gly Gly Lys Ala 485 490 495 Pro Leu Val Ala Glu Ala Glu Lys HisAla Gln Ser Leu Gln Glu Leu 500 505 510 Ala Lys Gln Leu Glu Glu Ile LysArg Asn Thr Ser Gly Asp Glu Ser 515 520 525 Val Arg Cys Val Val Asp AlaAla Thr Ala Tyr Glu Ser Ile Leu Asn 530 535 540 Ala Ile Arg Ala Ala GluAsp Ala Ala Gly Lys Ala Asp Ser Ala Ser 545 550 555 560 Glu Ser Ala PheGln Thr Val Ile Lys Glu Asp Leu Pro Arg Arg Ala 565 570 575 Lys Thr LeuSer Ser Asp Ser Glu Glu Leu Leu Asn Glu Ala Lys Met 580 585 590 Thr ArgLys Arg Leu Gln Gln Glu Ile Asn Pro Ala Leu Asn Ser Leu 595 600 605 GlnGln Thr Leu Lys Thr Val Ser Val Gln Lys Asp Leu Leu Asp Ala 610 615 620Asn Val Thr Ala Val Arg Asn Asp Leu Arg Gly Ile Gln Arg Gly Asp 625 630635 640 Ile Asp Ser Val Val Ser Gly Ala Lys Ser Met Val Arg Lys Ala Asn645 650 655 Gly Ile Thr Ser Glu Val Leu Asp Gly Leu Ser Pro Ile Gln ThrAsp 660 665 670 Leu Gly Arg Ile Lys Asp Ser Tyr Gly Ser Thr Arg His GluAsp Phe 675 680 685 Asn Lys Ala Leu Ile Asp Ala Asn Asn Ser Val Lys LysLeu Thr Lys 690 695 700 Lys Leu Pro Asp Leu Phe Val Lys Ile Glu Ser IleAsn Gln Gln Leu 705 710 715 720 Leu Pro Leu Gly Asn Ile Ser Asp Asn ValAsp Arg Ile Arg Glu Leu 725 730 735 Ile Thr Gln Ala Arg Asp Ala Ala AsnLys Val Ala Ile Pro Met Arg 740 745 750 Phe Asn Gly Lys Ser Gly Val GluVal Arg Leu Pro Asn Asp Leu Glu 755 760 765 Asp Leu Lys Gly Tyr Thr SerLeu Ser Leu Phe Leu Gln Arg Pro Asp 770 775 780 Leu Arg Glu Asn Gly GlyThr Glu Asp Met Phe Val Met Tyr Leu Gly 785 790 795 800 Asn Lys Asp AlaSer Lys Asp Tyr Ile Gly Met Ala Val Val Asp Gly 805 810 815 Gln Leu ThrCys Val Tyr Asn Leu Gly Asp Arg Glu Ala Glu Val Gln 820 825 830 Ile AspGln Val Leu Thr Glu Ser Glu Ser Gln Glu Ala Val Met Asp 835 840 845 ArgVal Lys Phe Gln Arg Ile Tyr Gln Phe Ala Lys Leu Asn Tyr Thr 850 855 860Lys Glu Ala Thr Ser Asn Lys Pro Lys Ala Pro Ala Val Tyr Asp Leu 865 870875 880 Glu Gly Gly Ser Ser Asn Thr Leu Leu Asn Leu Asp Pro Glu Asp Ala885 890 895 Val Phe Tyr Val Gly Gly Tyr Pro Pro Asp Phe Glu Leu Pro SerArg 900 905 910 Leu Arg Phe Pro Pro Tyr Lys Gly Cys Ile Glu Leu Asp AspLeu Asn 915 920 925 Glu Asn Val Leu Ser Leu Tyr Asn Phe Lys Thr Thr PheAsn Leu Asn 930 935 940 Thr Thr Glu Val Glu Pro Cys Arg Arg Arg Lys GluGlu Ser Asp Lys 945 950 955 960 Asn Tyr Phe Glu Gly Thr Gly Tyr Ala ArgIle Pro Thr Gln Pro Asn 965 970 975 Ala Pro Phe Pro Asn Phe Ile Gln ThrIle Gln Thr Thr Val Asp Arg 980 985 990 Gly Leu Leu Phe Phe Ala Glu AsnGln Asp Asn Phe Ile Ser Leu Asn 995 1000 1005 Ile Glu Asp Gly Asn LeuMet Val Arg Tyr Lys Leu Asn Ser Glu Pro 1010 1015 1020 Pro Lys Glu LysGly Ile Arg Asp Thr Ile Asn Asp Gly Lys Asp His 1025 1030 1035 1040 SerIle Leu Ile Thr Ile Gly Lys Leu Gln Lys Arg Met Trp Ile Asn 1045 10501055 Val Asn Glu Arg Ser Val Arg Ile Glu Gly Glu Ile Phe Asp Phe Ser1060 1065 1070 Thr Tyr Tyr Leu Gly Gly Ile Pro Ile Ala Ile Arg Glu ArgPhe Asn 1075 1080 1085 Ile Ser Thr Pro Ala Phe Gln Gly Cys Met Lys AsnLeu Lys Lys Thr 1090 1095 1100 Ser Gly Val Val Arg Leu Asn Asp Thr ValGly Val Thr Lys Lys Cys 1105 1110 1115 1120 Ser Glu Asp Trp Lys Leu ValArg Thr Ala Ser Phe Ser Arg Gly Gly 1125 1130 1135 Gln Met Ser Phe ThrAsn Leu Asp Val Pro Ser Thr Asp Arg Phe Gln 1140 1145 1150 Leu Ser PheGly Phe Gln Thr Phe Gln Pro Ser Gly Thr Leu Leu Asn 1155 1160 1165 HisGln Thr Arg Thr Ser Ser Leu Leu Val Thr Leu Glu Asp Gly His 1170 11751180 Ile Glu Leu Ser Thr Arg Asp Ser Asn Ile Pro Ile Phe Lys Ser Pro1185 1190 1195 1200 Gly Thr Tyr Met Asp Gly Leu Leu His His Val Ser ValIle Ser Asp 1205 1210 1215 Thr Ser Gly Leu Arg Leu Leu Ile Asp Asp GlnVal Leu Arg Arg Asn 1220 1225 1230 Gln Arg Leu Pro Ser Phe Ser Asn AlaGln Gln Ser Leu Arg Leu Gly 1235 1240 1245 Gly Gly His Phe Glu Gly CysIle Ser Asn Val Leu Val Gln Arg Phe 1250 1255 1260 Ser Gln Ser Pro GluVal Leu Asp Leu Ala Ser Lys Ser Thr Lys Lys 1265 1270 1275 1280 Asp AlaSer Leu Gly Gly Cys Ser Leu Asn Lys Pro Pro Phe Leu Met 1285 1290 1295Leu Phe Lys Ser Pro Lys Arg Phe Asn Lys Gly Arg Ile Phe Asn Val 13001305 1310 Asn Gln Leu Met Gln Asp Ala Pro Gln Ala Thr Arg Ser Thr GluAla 1315 1320 1325 Trp Gln Asp Gly Arg Ser Cys Leu Pro Pro Leu Asn ThrLys Ala Ser 1330 1335 1340 His Arg Ala Leu Gln Phe Gly Asp Ser Pro ThrSer His Leu Leu Leu 1345 1350 1355 1360 Lys Leu Pro Gln Glu Leu Leu LysPro Arg Ser Gln Phe Ser Leu Asp 1365 1370 1375 Ile Gln Thr Thr Ser ProLys Gly Leu Val Phe Tyr Ala Gly Thr Lys 1380 1385 1390 Asp Ser Phe LeuAla Leu Tyr Val Ala Asp Gly Arg Val Val Phe Ala 1395 1400 1405 Leu GlyAla Gly Gly Lys Lys Leu Arg Leu Arg Ser Lys Glu Arg Tyr 1410 1415 1420His Asp Gly Lys Trp His Thr Val Val Phe Gly Leu Asn Gly Gly Lys 14251430 1435 1440 Ala Arg Leu Val Val Asp Gly Leu Arg Ala Gln Glu Gly SerLeu Pro 1445 1450 1455 Gly Asn Ser Thr Ile Ser Pro Arg Glu Gln Val TyrLeu Gly Leu Pro 1460 1465 1470 Leu Ser Arg Lys Pro Lys Ser Leu Pro GlnHis Ser Phe Val Gly Cys 1475 1480 1485 Leu Arg Asp Phe Gln Leu Asn SerLys Pro Leu Asp Ser Pro Ser Ala 1490 1495 1500 Arg Phe Gly Val Ser ProCys Leu Gly Gly Ser Leu Glu Lys Gly Ile 1505 1510 1515 1520 Tyr Phe SerGln Gly Gly Gly His Val Ile Leu Ala Asn Ser Val Ser 1525 1530 1535 LeuGly Pro Glu Leu Lys Leu Thr Phe Ser Ile Arg Pro Arg Ser Leu 1540 15451550 Thr Gly Val Leu Ile His Val Gly Ser Gln Ser Gly Gln Arg Leu Ser1555 1560 1565 Val Tyr Met Glu Ala Gly Lys Val Thr Thr Ser Val Ser SerAsp Ala 1570 1575 1580 Gly Gly Ser Val Thr Ser Ile Thr Pro Lys Gln SerLeu Cys Asp Gly 1585 1590 1595 1600 Gln Trp His Ser Val Ala Val Ser IleLys Gln Arg Ile Leu His Leu 1605 1610 1615 Glu Leu Asp Thr Asp Ser SerTyr Thr Val Ala Pro Leu Ser Phe Ser 1620 1625 1630 Pro Asn Ser Thr ArgGly Ser Leu His Val Gly Gly Val Pro Asp Lys 1635 1640 1645 Leu Lys MetLeu Thr Leu Pro Val Trp Asn Ser Phe Phe Gly Cys Leu 1650 1655 1660 LysAsn Ile Gln Val Asn His Val Pro Val Pro Ile Thr Glu Ala Thr 1665 16701675 1680 Glu Val Gln Gly Ser Val Ser Leu Asn Gly Cys Pro Asp His 16851690 13 3930 DNA Homo sapiens CDS (121)..(3630) sig_peptide (121)..(171)13 gggcgggagg aggactgtat ctctggatgc ctggggcctg gtttcagggc ctgatttatt 60cctcttcctg ggagctcact caggaaaggt cctttctggg gatcacccca ttggctgaag 120atg aga cca ttc ttc ctc ttg tgt ttt gcc ctg cct ggc ctc ctg cat 168 MetArg Pro Phe Phe Leu Leu Cys Phe Ala Leu Pro Gly Leu Leu His 1 5 10 15gcc caa caa gcc tgc tcc cgt ggg gcc tgc tat cca cct gtt ggg gac 216 AlaGln Gln Ala Cys Ser Arg Gly Ala Cys Tyr Pro Pro Val Gly Asp 20 25 30 ctgctt gtt ggg agg acc cgg ttt ctc cga gct tca tct acc tgt gga 264 Leu LeuVal Gly Arg Thr Arg Phe Leu Arg Ala Ser Ser Thr Cys Gly 35 40 45 ctg accaag cct gag acc tac tgc acc cag tat ggc gag tgg cag atg 312 Leu Thr LysPro Glu Thr Tyr Cys Thr Gln Tyr Gly Glu Trp Gln Met 50 55 60 aaa tgc tgcaag tgt gac tcc agg cag cct cac aac tac tac agt cac 360 Lys Cys Cys LysCys Asp Ser Arg Gln Pro His Asn Tyr Tyr Ser His 65 70 75 80 cga gta gagaat gtg gct tca tcc tcc ggc ccc atg cgc tgg tgg cag 408 Arg Val Glu AsnVal Ala Ser Ser Ser Gly Pro Met Arg Trp Trp Gln 85 90 95 tcc cag aat gatgtg aac cct gtc tct ctg cag ctg gac ctg gac agg 456 Ser Gln Asn Asp ValAsn Pro Val Ser Leu Gln Leu Asp Leu Asp Arg 100 105 110 aga ttc cag cttcaa gaa gtc atg atg gag ttc cga ggg ccc atg cct 504 Arg Phe Gln Leu GlnGlu Val Met Met Glu Phe Arg Gly Pro Met Pro 115 120 125 gcc ggc atg ctgatt gag cgc tcc tca gac ttc ggt aag acc tgg cga 552 Ala Gly Met Leu IleGlu Arg Ser Ser Asp Phe Gly Lys Thr Trp Arg 130 135 140 gtg tac cag tacctg gct gcc gac tgc acc tcc acc ttc cct cgg gtc 600 Val Tyr Gln Tyr LeuAla Ala Asp Cys Thr Ser Thr Phe Pro Arg Val 145 150 155 160 cgc cag ggtcgg cct cag agc tgg cag gat gtt cgg tgc cag tcc ctg 648 Arg Gln Gly ArgPro Gln Ser Trp Gln Asp Val Arg Cys Gln Ser Leu 165 170 175 cct cag aggcct aat gca cgc cta aat ggg ggg aag gtc caa ctt aac 696 Pro Gln Arg ProAsn Ala Arg Leu Asn Gly Gly Lys Val Gln Leu Asn 180 185 190 ctt atg gattta gtg tct ggg att cca gca act caa agt caa aaa att 744 Leu Met Asp LeuVal Ser Gly Ile Pro Ala Thr Gln Ser Gln Lys Ile 195 200 205 caa gag gtgggg gag atc aca aac ttg aga gtc aat ttc acc agg ctg 792 Gln Glu Val GlyGlu Ile Thr Asn Leu Arg Val Asn Phe Thr Arg Leu 210 215 220 gcc cct gtgccc caa agg ggc tac cac cct ccc agc gcc tac tat gct 840 Ala Pro Val ProGln Arg Gly Tyr His Pro Pro Ser Ala Tyr Tyr Ala 225 230 235 240 gtg tcccag ctc cgt ctg cag ggg agc tgc ttc tgt cac ggc cat gct 888 Val Ser GlnLeu Arg Leu Gln Gly Ser Cys Phe Cys His Gly His Ala 245 250 255 gat cgctgc gca ccc aag cct ggg gcc tct gca ggc tcc acc gct gtg 936 Asp Arg CysAla Pro Lys Pro Gly Ala Ser Ala Gly Ser Thr Ala Val 260 265 270 cag gtccac gat gtc tgc gtc tgc cag cac aac act gcc ggc cca aat 984 Gln Val HisAsp Val Cys Val Cys Gln His Asn Thr Ala Gly Pro Asn 275 280 285 tgt gagcgc tgt gca ccc ttc tac aac aac cgg ccc tgg aga ccg gcg 1032 Cys Glu ArgCys Ala Pro Phe Tyr Asn Asn Arg Pro Trp Arg Pro Ala 290 295 300 gag ggccag gac gcc cat gaa tgc caa agg tgc gac tgc aat ggg cac 1080 Glu Gly GlnAsp Ala His Glu Cys Gln Arg Cys Asp Cys Asn Gly His 305 310 315 320 tcagag aca tgt cac ttt gac ccc gct gtg ttt gcc gcc agc cag ggg 1128 Ser GluThr Cys His Phe Asp Pro Ala Val Phe Ala Ala Ser Gln Gly 325 330 335 gcatat gga ggt gtg tgt gac aat tgc cgg gac cac acc gaa ggc aag 1176 Ala TyrGly Gly Val Cys Asp Asn Cys Arg Asp His Thr Glu Gly Lys 340 345 350 aactgt gag cgg tgt cag ctg cac tat ttc cgg aac cgg cgc ccg gga 1224 Asn CysGlu Arg Cys Gln Leu His Tyr Phe Arg Asn Arg Arg Pro Gly 355 360 365 gcttcc att cag gag acc tgc atc tcc tgc gag tgt gat ccg gat ggg 1272 Ala SerIle Gln Glu Thr Cys Ile Ser Cys Glu Cys Asp Pro Asp Gly 370 375 380 gcagtc gca ggg gct ccc tgt gac cca gtg acc ggg cag tgt gtg tgc 1320 Ala ValAla Gly Ala Pro Cys Asp Pro Val Thr Gly Gln Cys Val Cys 385 390 395 400aag gag cat gtg cag gga gag cgc tgt gac cta tgc aag ccg ggc ttc 1368 LysGlu His Val Gln Gly Glu Arg Cys Asp Leu Cys Lys Pro Gly Phe 405 410 415act gga ctc acc tac gcc aac ccg cga cgg tgc cac cgc tgt gac tgc 1416 ThrGly Leu Thr Tyr Ala Asn Pro Arg Arg Cys His Arg Cys Asp Cys 420 425 430aac atc ctg ggg tcc cgg gag atg ccg tgt gac gag gag agt ggg cgc 1464 AsnIle Leu Gly Ser Arg Glu Met Pro Cys Asp Glu Glu Ser Gly Arg 435 440 445tgc ctt tgt ctg ccc aac gtg gtg ggt ccc aaa tgt gac cag tgt gct 1512 CysLeu Cys Leu Pro Asn Val Val Gly Pro Lys Cys Asp Gln Cys Ala 450 455 460ccc tac cac tgg aag ctg gcc agt ggc cag ggc tgt gaa ccg tgt gcc 1560 ProTyr His Trp Lys Leu Ala Ser Gly Gln Gly Cys Glu Pro Cys Ala 465 470 475480 tgc gac ccg cac aac tcc ctc agc cca cag tgc aac cag ttc aca ggg 1608Cys Asp Pro His Asn Ser Leu Ser Pro Gln Cys Asn Gln Phe Thr Gly 485 490495 cag tgc ccc tgt cgg gaa ggc ttt ggt ggc ctg atg tgc agc gct gca 1656Gln Cys Pro Cys Arg Glu Gly Phe Gly Gly Leu Met Cys Ser Ala Ala 500 505510 gcc atc cgc cag tgt cca gac cgg acc tat gga gac gtg gcc aca gga 1704Ala Ile Arg Gln Cys Pro Asp Arg Thr Tyr Gly Asp Val Ala Thr Gly 515 520525 tgc cga gcc tgt gac tgt gat ttc cgg gga aca gag ggc ccg ggc tgc 1752Cys Arg Ala Cys Asp Cys Asp Phe Arg Gly Thr Glu Gly Pro Gly Cys 530 535540 gac aag gca tca ggc cgc tgc ctc tgc cgc cct ggc ttg acc ggg ccc 1800Asp Lys Ala Ser Gly Arg Cys Leu Cys Arg Pro Gly Leu Thr Gly Pro 545 550555 560 cgc tgt gac cag tgc cag cga ggc tac tgc aat cgc tac ccg gtg tgc1848 Arg Cys Asp Gln Cys Gln Arg Gly Tyr Cys Asn Arg Tyr Pro Val Cys 565570 575 gtg gcc tgc cac cct tgc ttc cag acc tat gat gcg gac ctc cgg gag1896 Val Ala Cys His Pro Cys Phe Gln Thr Tyr Asp Ala Asp Leu Arg Glu 580585 590 cag gcc ctg cgc ttt ggt aga ctc ccg aat gcc acc gcc agc ctg tgg1944 Gln Ala Leu Arg Phe Gly Arg Leu Pro Asn Ala Thr Ala Ser Leu Trp 595600 605 tca ggg cct ggg ctg gag gac cgt ggc ctg gcc tcc cgg atc cta gat1992 Ser Gly Pro Gly Leu Glu Asp Arg Gly Leu Ala Ser Arg Ile Leu Asp 610615 620 gca aag agt aag att gag cag atc cga gca gtt ctc agc agc ccc gca2040 Ala Lys Ser Lys Ile Glu Gln Ile Arg Ala Val Leu Ser Ser Pro Ala 625630 635 640 gtc aca gag cag gag gtg gct cag gtg gcc agt gcc atc ctc tccctc 2088 Val Thr Glu Gln Glu Val Ala Gln Val Ala Ser Ala Ile Leu Ser Leu645 650 655 agg cga act ctc cag ggc ctg cag ctg gat ctg ccc ctg gag gaggag 2136 Arg Arg Thr Leu Gln Gly Leu Gln Leu Asp Leu Pro Leu Glu Glu Glu660 665 670 acg ttg tcc ctt ccg aga gac ctg gag agt ctt gac aga agc ttcaat 2184 Thr Leu Ser Leu Pro Arg Asp Leu Glu Ser Leu Asp Arg Ser Phe Asn675 680 685 ggt ctc ctt act atg tat cag agg aag agg gag cag ttt gaa aaaata 2232 Gly Leu Leu Thr Met Tyr Gln Arg Lys Arg Glu Gln Phe Glu Lys Ile690 695 700 agc agt gct gat cct tca gga gcc ttc cgg atg ctg agc aca gcctac 2280 Ser Ser Ala Asp Pro Ser Gly Ala Phe Arg Met Leu Ser Thr Ala Tyr705 710 715 720 gag cag tca gcc cag gct gct cag cag gtc tcc gac agc tcgcgc ctt 2328 Glu Gln Ser Ala Gln Ala Ala Gln Gln Val Ser Asp Ser Ser ArgLeu 725 730 735 ttg gac cag ctc agg gac agc cgg aga gag gca gag agg ctggtg cgg 2376 Leu Asp Gln Leu Arg Asp Ser Arg Arg Glu Ala Glu Arg Leu ValArg 740 745 750 cag gcg gga gga gga gga ggc acc ggc agc ccc aag ctt gtggcc ctg 2424 Gln Ala Gly Gly Gly Gly Gly Thr Gly Ser Pro Lys Leu Val AlaLeu 755 760 765 agg ttg gag atg tct tcg ttg cct gac ctg aca ccc acc ttcaac aag 2472 Arg Leu Glu Met Ser Ser Leu Pro Asp Leu Thr Pro Thr Phe AsnLys 770 775 780 ctc tgt ggc aac tcc agg cag atg gct tgc acc cca ata tcatgc cct 2520 Leu Cys Gly Asn Ser Arg Gln Met Ala Cys Thr Pro Ile Ser CysPro 785 790 795 800 ggt gag cta tgt ccc caa gac aat ggc aca gcc tgt gcgtcc cgc tgc 2568 Gly Glu Leu Cys Pro Gln Asp Asn Gly Thr Ala Cys Ala SerArg Cys 805 810 815 agg ggt gtc ctt ccc agg gcc ggt ggg gcc ttc ttg atggcg ggg cag 2616 Arg Gly Val Leu Pro Arg Ala Gly Gly Ala Phe Leu Met AlaGly Gln 820 825 830 gtg gct gag cag ctg cgg ggc ttc aat gcc cag ctc cagcgg acc agg 2664 Val Ala Glu Gln Leu Arg Gly Phe Asn Ala Gln Leu Gln ArgThr Arg 835 840 845 cag atg att agg gca gcc gag gaa tct gcc tca cag attcaa tcc agt 2712 Gln Met Ile Arg Ala Ala Glu Glu Ser Ala Ser Gln Ile GlnSer Ser 850 855 860 gcc cag cgc ttg gag acc cag gtg agc gcc agc cgc tcccag atg gag 2760 Ala Gln Arg Leu Glu Thr Gln Val Ser Ala Ser Arg Ser GlnMet Glu 865 870 875 880 gaa gat gtc aga cgc aca cgg ctc cta atc cag caggtc cgg gac ttc 2808 Glu Asp Val Arg Arg Thr Arg Leu Leu Ile Gln Gln ValArg Asp Phe 885 890 895 cta aca gac ccc gac act gat gca gcc act atc caggag gtc agc gag 2856 Leu Thr Asp Pro Asp Thr Asp Ala Ala Thr Ile Gln GluVal Ser Glu 900 905 910 gcc gtg ctg gcc ctg tgg ctg ccc aca gac tca gctact gtt ctg cag 2904 Ala Val Leu Ala Leu Trp Leu Pro Thr Asp Ser Ala ThrVal Leu Gln 915 920 925 aag atg aat gag atc cag gcc att gca gcc agg ctcccc aac gtg gac 2952 Lys Met Asn Glu Ile Gln Ala Ile Ala Ala Arg Leu ProAsn Val Asp 930 935 940 ttg gtg ctg tcc cag acc aag cag gac att gcg cgtgcc cgc cgg ttg 3000 Leu Val Leu Ser Gln Thr Lys Gln Asp Ile Ala Arg AlaArg Arg Leu 945 950 955 960 cag gct gag gct gag gaa gcc agg agc cga gcccat gca gtg gag ggc 3048 Gln Ala Glu Ala Glu Glu Ala Arg Ser Arg Ala HisAla Val Glu Gly 965 970 975 cag gtg gag gat gtg gtt ggg aac ctg cgg cagggg aca gtg gca ctg 3096 Gln Val Glu Asp Val Val Gly Asn Leu Arg Gln GlyThr Val Ala Leu 980 985 990 cag gaa gct cag gac acc atg caa ggc acc agccgg tcc ctt cgg ctt 3144 Gln Glu Ala Gln Asp Thr Met Gln Gly Thr Ser ArgSer Leu Arg Leu 995 1000 1005 atc cag gac agg gtt gct gag gtt cag caggta ctg cgg cca gca gaa 3192 Ile Gln Asp Arg Val Ala Glu Val Gln Gln ValLeu Arg Pro Ala Glu 1010 1015 1020 aag ctg gtg aca agc atg acc aag cagctg ggt gac ttc tgg aca cgg 3240 Lys Leu Val Thr Ser Met Thr Lys Gln LeuGly Asp Phe Trp Thr Arg 1025 1030 1035 1040 atg gag gag ctc cgc cac caagcc cgg cag cag ggg gca gag gca gtc 3288 Met Glu Glu Leu Arg His Gln AlaArg Gln Gln Gly Ala Glu Ala Val 1045 1050 1055 cag gcc cag cag ctt gcggaa ggt gcc agc gag cag gca ttg agt gcc 3336 Gln Ala Gln Gln Leu Ala GluGly Ala Ser Glu Gln Ala Leu Ser Ala 1060 1065 1070 caa gag gga ttt gagaga ata aaa caa aag tat gct gag ttg aag gac 3384 Gln Glu Gly Phe Glu ArgIle Lys Gln Lys Tyr Ala Glu Leu Lys Asp 1075 1080 1085 cgg ttg ggt cagagt tcc atg ctg ggt gag cag ggt gcc cgg atc cag 3432 Arg Leu Gly Gln SerSer Met Leu Gly Glu Gln Gly Ala Arg Ile Gln 1090 1095 1100 agt gtg aagaca gag gca gag gag ctg ttt ggg gag acc atg gag atg 3480 Ser Val Lys ThrGlu Ala Glu Glu Leu Phe Gly Glu Thr Met Glu Met 1105 1110 1115 1120 atggac agg atg aaa gac atg gag ttg gag ctg ctg cgg ggc agc cag 3528 Met AspArg Met Lys Asp Met Glu Leu Glu Leu Leu Arg Gly Ser Gln 1125 1130 1135gcc atc atg ctg cgc tca gcg gac ctg aca gga ctg gag aag cgt gtg 3576 AlaIle Met Leu Arg Ser Ala Asp Leu Thr Gly Leu Glu Lys Arg Val 1140 11451150 gag cag atc cgt gac cac atc aat ggg cgc gtg ctc tac tat gcc acc3624 Glu Gln Ile Arg Asp His Ile Asn Gly Arg Val Leu Tyr Tyr Ala Thr1155 1160 1165 tgc aag tgatgctaca cgttccagcc cgttgcccca ctcatctgcgcgctttgctt 3680 Cys Lys 1170 ttggttgggg ggcagattgg gttggaatgc tttccatctccaggagactt tcatgtagcc 3740 caaagtacag cctggaccac ccctggtgtg tgtagctagtaagattaccc tgagctgcag 3800 ctgagcctga gccaatggga cagttacact tgacagacaaagatggtgga gattggcatg 3860 ccattgaaac taagagctct caagtcaagg aagctgggctgggcagtatc ccccgccttt 3920 agttctccac 3930 14 1170 PRT Homo sapiens 14Met Arg Pro Phe Phe Leu Leu Cys Phe Ala Leu Pro Gly Leu Leu His 1 5 1015 Ala Gln Gln Ala Cys Ser Arg Gly Ala Cys Tyr Pro Pro Val Gly Asp 20 2530 Leu Leu Val Gly Arg Thr Arg Phe Leu Arg Ala Ser Ser Thr Cys Gly 35 4045 Leu Thr Lys Pro Glu Thr Tyr Cys Thr Gln Tyr Gly Glu Trp Gln Met 50 5560 Lys Cys Cys Lys Cys Asp Ser Arg Gln Pro His Asn Tyr Tyr Ser His 65 7075 80 Arg Val Glu Asn Val Ala Ser Ser Ser Gly Pro Met Arg Trp Trp Gln 8590 95 Ser Gln Asn Asp Val Asn Pro Val Ser Leu Gln Leu Asp Leu Asp Arg100 105 110 Arg Phe Gln Leu Gln Glu Val Met Met Glu Phe Arg Gly Pro MetPro 115 120 125 Ala Gly Met Leu Ile Glu Arg Ser Ser Asp Phe Gly Lys ThrTrp Arg 130 135 140 Val Tyr Gln Tyr Leu Ala Ala Asp Cys Thr Ser Thr PhePro Arg Val 145 150 155 160 Arg Gln Gly Arg Pro Gln Ser Trp Gln Asp ValArg Cys Gln Ser Leu 165 170 175 Pro Gln Arg Pro Asn Ala Arg Leu Asn GlyGly Lys Val Gln Leu Asn 180 185 190 Leu Met Asp Leu Val Ser Gly Ile ProAla Thr Gln Ser Gln Lys Ile 195 200 205 Gln Glu Val Gly Glu Ile Thr AsnLeu Arg Val Asn Phe Thr Arg Leu 210 215 220 Ala Pro Val Pro Gln Arg GlyTyr His Pro Pro Ser Ala Tyr Tyr Ala 225 230 235 240 Val Ser Gln Leu ArgLeu Gln Gly Ser Cys Phe Cys His Gly His Ala 245 250 255 Asp Arg Cys AlaPro Lys Pro Gly Ala Ser Ala Gly Ser Thr Ala Val 260 265 270 Gln Val HisAsp Val Cys Val Cys Gln His Asn Thr Ala Gly Pro Asn 275 280 285 Cys GluArg Cys Ala Pro Phe Tyr Asn Asn Arg Pro Trp Arg Pro Ala 290 295 300 GluGly Gln Asp Ala His Glu Cys Gln Arg Cys Asp Cys Asn Gly His 305 310 315320 Ser Glu Thr Cys His Phe Asp Pro Ala Val Phe Ala Ala Ser Gln Gly 325330 335 Ala Tyr Gly Gly Val Cys Asp Asn Cys Arg Asp His Thr Glu Gly Lys340 345 350 Asn Cys Glu Arg Cys Gln Leu His Tyr Phe Arg Asn Arg Arg ProGly 355 360 365 Ala Ser Ile Gln Glu Thr Cys Ile Ser Cys Glu Cys Asp ProAsp Gly 370 375 380 Ala Val Ala Gly Ala Pro Cys Asp Pro Val Thr Gly GlnCys Val Cys 385 390 395 400 Lys Glu His Val Gln Gly Glu Arg Cys Asp LeuCys Lys Pro Gly Phe 405 410 415 Thr Gly Leu Thr Tyr Ala Asn Pro Arg ArgCys His Arg Cys Asp Cys 420 425 430 Asn Ile Leu Gly Ser Arg Glu Met ProCys Asp Glu Glu Ser Gly Arg 435 440 445 Cys Leu Cys Leu Pro Asn Val ValGly Pro Lys Cys Asp Gln Cys Ala 450 455 460 Pro Tyr His Trp Lys Leu AlaSer Gly Gln Gly Cys Glu Pro Cys Ala 465 470 475 480 Cys Asp Pro His AsnSer Leu Ser Pro Gln Cys Asn Gln Phe Thr Gly 485 490 495 Gln Cys Pro CysArg Glu Gly Phe Gly Gly Leu Met Cys Ser Ala Ala 500 505 510 Ala Ile ArgGln Cys Pro Asp Arg Thr Tyr Gly Asp Val Ala Thr Gly 515 520 525 Cys ArgAla Cys Asp Cys Asp Phe Arg Gly Thr Glu Gly Pro Gly Cys 530 535 540 AspLys Ala Ser Gly Arg Cys Leu Cys Arg Pro Gly Leu Thr Gly Pro 545 550 555560 Arg Cys Asp Gln Cys Gln Arg Gly Tyr Cys Asn Arg Tyr Pro Val Cys 565570 575 Val Ala Cys His Pro Cys Phe Gln Thr Tyr Asp Ala Asp Leu Arg Glu580 585 590 Gln Ala Leu Arg Phe Gly Arg Leu Pro Asn Ala Thr Ala Ser LeuTrp 595 600 605 Ser Gly Pro Gly Leu Glu Asp Arg Gly Leu Ala Ser Arg IleLeu Asp 610 615 620 Ala Lys Ser Lys Ile Glu Gln Ile Arg Ala Val Leu SerSer Pro Ala 625 630 635 640 Val Thr Glu Gln Glu Val Ala Gln Val Ala SerAla Ile Leu Ser Leu 645 650 655 Arg Arg Thr Leu Gln Gly Leu Gln Leu AspLeu Pro Leu Glu Glu Glu 660 665 670 Thr Leu Ser Leu Pro Arg Asp Leu GluSer Leu Asp Arg Ser Phe Asn 675 680 685 Gly Leu Leu Thr Met Tyr Gln ArgLys Arg Glu Gln Phe Glu Lys Ile 690 695 700 Ser Ser Ala Asp Pro Ser GlyAla Phe Arg Met Leu Ser Thr Ala Tyr 705 710 715 720 Glu Gln Ser Ala GlnAla Ala Gln Gln Val Ser Asp Ser Ser Arg Leu 725 730 735 Leu Asp Gln LeuArg Asp Ser Arg Arg Glu Ala Glu Arg Leu Val Arg 740 745 750 Gln Ala GlyGly Gly Gly Gly Thr Gly Ser Pro Lys Leu Val Ala Leu 755 760 765 Arg LeuGlu Met Ser Ser Leu Pro Asp Leu Thr Pro Thr Phe Asn Lys 770 775 780 LeuCys Gly Asn Ser Arg Gln Met Ala Cys Thr Pro Ile Ser Cys Pro 785 790 795800 Gly Glu Leu Cys Pro Gln Asp Asn Gly Thr Ala Cys Ala Ser Arg Cys 805810 815 Arg Gly Val Leu Pro Arg Ala Gly Gly Ala Phe Leu Met Ala Gly Gln820 825 830 Val Ala Glu Gln Leu Arg Gly Phe Asn Ala Gln Leu Gln Arg ThrArg 835 840 845 Gln Met Ile Arg Ala Ala Glu Glu Ser Ala Ser Gln Ile GlnSer Ser 850 855 860 Ala Gln Arg Leu Glu Thr Gln Val Ser Ala Ser Arg SerGln Met Glu 865 870 875 880 Glu Asp Val Arg Arg Thr Arg Leu Leu Ile GlnGln Val Arg Asp Phe 885 890 895 Leu Thr Asp Pro Asp Thr Asp Ala Ala ThrIle Gln Glu Val Ser Glu 900 905 910 Ala Val Leu Ala Leu Trp Leu Pro ThrAsp Ser Ala Thr Val Leu Gln 915 920 925 Lys Met Asn Glu Ile Gln Ala IleAla Ala Arg Leu Pro Asn Val Asp 930 935 940 Leu Val Leu Ser Gln Thr LysGln Asp Ile Ala Arg Ala Arg Arg Leu 945 950 955 960 Gln Ala Glu Ala GluGlu Ala Arg Ser Arg Ala His Ala Val Glu Gly 965 970 975 Gln Val Glu AspVal Val Gly Asn Leu Arg Gln Gly Thr Val Ala Leu 980 985 990 Gln Glu AlaGln Asp Thr Met Gln Gly Thr Ser Arg Ser Leu Arg Leu 995 1000 1005 IleGln Asp Arg Val Ala Glu Val Gln Gln Val Leu Arg Pro Ala Glu 1010 10151020 Lys Leu Val Thr Ser Met Thr Lys Gln Leu Gly Asp Phe Trp Thr Arg1025 1030 1035 1040 Met Glu Glu Leu Arg His Gln Ala Arg Gln Gln Gly AlaGlu Ala Val 1045 1050 1055 Gln Ala Gln Gln Leu Ala Glu Gly Ala Ser GluGln Ala Leu Ser Ala 1060 1065 1070 Gln Glu Gly Phe Glu Arg Ile Lys GlnLys Tyr Ala Glu Leu Lys Asp 1075 1080 1085 Arg Leu Gly Gln Ser Ser MetLeu Gly Glu Gln Gly Ala Arg Ile Gln 1090 1095 1100 Ser Val Lys Thr GluAla Glu Glu Leu Phe Gly Glu Thr Met Glu Met 1105 1110 1115 1120 Met AspArg Met Lys Asp Met Glu Leu Glu Leu Leu Arg Gly Ser Gln 1125 1130 1135Ala Ile Met Leu Arg Ser Ala Asp Leu Thr Gly Leu Glu Lys Arg Val 11401145 1150 Glu Gln Ile Arg Asp His Ile Asn Gly Arg Val Leu Tyr Tyr AlaThr 1155 1160 1165 Cys Lys 1170 15 3759 DNA Homo sapiens CDS (1)..(3459)15 caa caa gcc tgc tcc cgt ggg gcc tgc tat cca cct gtt ggg gac ctg 48Gln Gln Ala Cys Ser Arg Gly Ala Cys Tyr Pro Pro Val Gly Asp Leu 1 5 1015 ctt gtt ggg agg acc cgg ttt ctc cga gct tca tct acc tgt gga ctg 96Leu Val Gly Arg Thr Arg Phe Leu Arg Ala Ser Ser Thr Cys Gly Leu 20 25 30acc aag cct gag acc tac tgc acc cag tat ggc gag tgg cag atg aaa 144 ThrLys Pro Glu Thr Tyr Cys Thr Gln Tyr Gly Glu Trp Gln Met Lys 35 40 45 tgctgc aag tgt gac tcc agg cag cct cac aac tac tac agt cac cga 192 Cys CysLys Cys Asp Ser Arg Gln Pro His Asn Tyr Tyr Ser His Arg 50 55 60 gta gagaat gtg gct tca tcc tcc ggc ccc atg cgc tgg tgg cag tcc 240 Val Glu AsnVal Ala Ser Ser Ser Gly Pro Met Arg Trp Trp Gln Ser 65 70 75 80 cag aatgat gtg aac cct gtc tct ctg cag ctg gac ctg gac agg aga 288 Gln Asn AspVal Asn Pro Val Ser Leu Gln Leu Asp Leu Asp Arg Arg 85 90 95 ttc cag cttcaa gaa gtc atg atg gag ttc cga ggg ccc atg cct gcc 336 Phe Gln Leu GlnGlu Val Met Met Glu Phe Arg Gly Pro Met Pro Ala 100 105 110 ggc atg ctgatt gag cgc tcc tca gac ttc ggt aag acc tgg cga gtg 384 Gly Met Leu IleGlu Arg Ser Ser Asp Phe Gly Lys Thr Trp Arg Val 115 120 125 tac cag tacctg gct gcc gac tgc acc tcc acc ttc cct cgg gtc cgc 432 Tyr Gln Tyr LeuAla Ala Asp Cys Thr Ser Thr Phe Pro Arg Val Arg 130 135 140 cag ggt cggcct cag agc tgg cag gat gtt cgg tgc cag tcc ctg cct 480 Gln Gly Arg ProGln Ser Trp Gln Asp Val Arg Cys Gln Ser Leu Pro 145 150 155 160 cag aggcct aat gca cgc cta aat ggg ggg aag gtc caa ctt aac ctt 528 Gln Arg ProAsn Ala Arg Leu Asn Gly Gly Lys Val Gln Leu Asn Leu 165 170 175 atg gattta gtg tct ggg att cca gca act caa agt caa aaa att caa 576 Met Asp LeuVal Ser Gly Ile Pro Ala Thr Gln Ser Gln Lys Ile Gln 180 185 190 gag gtgggg gag atc aca aac ttg aga gtc aat ttc acc agg ctg gcc 624 Glu Val GlyGlu Ile Thr Asn Leu Arg Val Asn Phe Thr Arg Leu Ala 195 200 205 cct gtgccc caa agg ggc tac cac cct ccc agc gcc tac tat gct gtg 672 Pro Val ProGln Arg Gly Tyr His Pro Pro Ser Ala Tyr Tyr Ala Val 210 215 220 tcc cagctc cgt ctg cag ggg agc tgc ttc tgt cac ggc cat gct gat 720 Ser Gln LeuArg Leu Gln Gly Ser Cys Phe Cys His Gly His Ala Asp 225 230 235 240 cgctgc gca ccc aag cct ggg gcc tct gca ggc tcc acc gct gtg cag 768 Arg CysAla Pro Lys Pro Gly Ala Ser Ala Gly Ser Thr Ala Val Gln 245 250 255 gtccac gat gtc tgc gtc tgc cag cac aac act gcc ggc cca aat tgt 816 Val HisAsp Val Cys Val Cys Gln His Asn Thr Ala Gly Pro Asn Cys 260 265 270 gagcgc tgt gca ccc ttc tac aac aac cgg ccc tgg aga ccg gcg gag 864 Glu ArgCys Ala Pro Phe Tyr Asn Asn Arg Pro Trp Arg Pro Ala Glu 275 280 285 ggccag gac gcc cat gaa tgc caa agg tgc gac tgc aat ggg cac tca 912 Gly GlnAsp Ala His Glu Cys Gln Arg Cys Asp Cys Asn Gly His Ser 290 295 300 gagaca tgt cac ttt gac ccc gct gtg ttt gcc gcc agc cag ggg gca 960 Glu ThrCys His Phe Asp Pro Ala Val Phe Ala Ala Ser Gln Gly Ala 305 310 315 320tat gga ggt gtg tgt gac aat tgc cgg gac cac acc gaa ggc aag aac 1008 TyrGly Gly Val Cys Asp Asn Cys Arg Asp His Thr Glu Gly Lys Asn 325 330 335tgt gag cgg tgt cag ctg cac tat ttc cgg aac cgg cgc ccg gga gct 1056 CysGlu Arg Cys Gln Leu His Tyr Phe Arg Asn Arg Arg Pro Gly Ala 340 345 350tcc att cag gag acc tgc atc tcc tgc gag tgt gat ccg gat ggg gca 1104 SerIle Gln Glu Thr Cys Ile Ser Cys Glu Cys Asp Pro Asp Gly Ala 355 360 365gtc gca ggg gct ccc tgt gac cca gtg acc ggg cag tgt gtg tgc aag 1152 ValAla Gly Ala Pro Cys Asp Pro Val Thr Gly Gln Cys Val Cys Lys 370 375 380gag cat gtg cag gga gag cgc tgt gac cta tgc aag ccg ggc ttc act 1200 GluHis Val Gln Gly Glu Arg Cys Asp Leu Cys Lys Pro Gly Phe Thr 385 390 395400 gga ctc acc tac gcc aac ccg cga cgg tgc cac cgc tgt gac tgc aac 1248Gly Leu Thr Tyr Ala Asn Pro Arg Arg Cys His Arg Cys Asp Cys Asn 405 410415 atc ctg ggg tcc cgg gag atg ccg tgt gac gag gag agt ggg cgc tgc 1296Ile Leu Gly Ser Arg Glu Met Pro Cys Asp Glu Glu Ser Gly Arg Cys 420 425430 ctt tgt ctg ccc aac gtg gtg ggt ccc aaa tgt gac cag tgt gct ccc 1344Leu Cys Leu Pro Asn Val Val Gly Pro Lys Cys Asp Gln Cys Ala Pro 435 440445 tac cac tgg aag ctg gcc agt ggc cag ggc tgt gaa ccg tgt gcc tgc 1392Tyr His Trp Lys Leu Ala Ser Gly Gln Gly Cys Glu Pro Cys Ala Cys 450 455460 gac ccg cac aac tcc ctc agc cca cag tgc aac cag ttc aca ggg cag 1440Asp Pro His Asn Ser Leu Ser Pro Gln Cys Asn Gln Phe Thr Gly Gln 465 470475 480 tgc ccc tgt cgg gaa ggc ttt ggt ggc ctg atg tgc agc gct gca gcc1488 Cys Pro Cys Arg Glu Gly Phe Gly Gly Leu Met Cys Ser Ala Ala Ala 485490 495 atc cgc cag tgt cca gac cgg acc tat gga gac gtg gcc aca gga tgc1536 Ile Arg Gln Cys Pro Asp Arg Thr Tyr Gly Asp Val Ala Thr Gly Cys 500505 510 cga gcc tgt gac tgt gat ttc cgg gga aca gag ggc ccg ggc tgc gac1584 Arg Ala Cys Asp Cys Asp Phe Arg Gly Thr Glu Gly Pro Gly Cys Asp 515520 525 aag gca tca ggc cgc tgc ctc tgc cgc cct ggc ttg acc ggg ccc cgc1632 Lys Ala Ser Gly Arg Cys Leu Cys Arg Pro Gly Leu Thr Gly Pro Arg 530535 540 tgt gac cag tgc cag cga ggc tac tgc aat cgc tac ccg gtg tgc gtg1680 Cys Asp Gln Cys Gln Arg Gly Tyr Cys Asn Arg Tyr Pro Val Cys Val 545550 555 560 gcc tgc cac cct tgc ttc cag acc tat gat gcg gac ctc cgg gagcag 1728 Ala Cys His Pro Cys Phe Gln Thr Tyr Asp Ala Asp Leu Arg Glu Gln565 570 575 gcc ctg cgc ttt ggt aga ctc ccg aat gcc acc gcc agc ctg tggtca 1776 Ala Leu Arg Phe Gly Arg Leu Pro Asn Ala Thr Ala Ser Leu Trp Ser580 585 590 ggg cct ggg ctg gag gac cgt ggc ctg gcc tcc cgg atc cta gatgca 1824 Gly Pro Gly Leu Glu Asp Arg Gly Leu Ala Ser Arg Ile Leu Asp Ala595 600 605 aag agt aag att gag cag atc cga gca gtt ctc agc agc ccc gcagtc 1872 Lys Ser Lys Ile Glu Gln Ile Arg Ala Val Leu Ser Ser Pro Ala Val610 615 620 aca gag cag gag gtg gct cag gtg gcc agt gcc atc ctc tcc ctcagg 1920 Thr Glu Gln Glu Val Ala Gln Val Ala Ser Ala Ile Leu Ser Leu Arg625 630 635 640 cga act ctc cag ggc ctg cag ctg gat ctg ccc ctg gag gaggag acg 1968 Arg Thr Leu Gln Gly Leu Gln Leu Asp Leu Pro Leu Glu Glu GluThr 645 650 655 ttg tcc ctt ccg aga gac ctg gag agt ctt gac aga agc ttcaat ggt 2016 Leu Ser Leu Pro Arg Asp Leu Glu Ser Leu Asp Arg Ser Phe AsnGly 660 665 670 ctc ctt act atg tat cag agg aag agg gag cag ttt gaa aaaata agc 2064 Leu Leu Thr Met Tyr Gln Arg Lys Arg Glu Gln Phe Glu Lys IleSer 675 680 685 agt gct gat cct tca gga gcc ttc cgg atg ctg agc aca gcctac gag 2112 Ser Ala Asp Pro Ser Gly Ala Phe Arg Met Leu Ser Thr Ala TyrGlu 690 695 700 cag tca gcc cag gct gct cag cag gtc tcc gac agc tcg cgcctt ttg 2160 Gln Ser Ala Gln Ala Ala Gln Gln Val Ser Asp Ser Ser Arg LeuLeu 705 710 715 720 gac cag ctc agg gac agc cgg aga gag gca gag agg ctggtg cgg cag 2208 Asp Gln Leu Arg Asp Ser Arg Arg Glu Ala Glu Arg Leu ValArg Gln 725 730 735 gcg gga gga gga gga ggc acc ggc agc ccc aag ctt gtggcc ctg agg 2256 Ala Gly Gly Gly Gly Gly Thr Gly Ser Pro Lys Leu Val AlaLeu Arg 740 745 750 ttg gag atg tct tcg ttg cct gac ctg aca ccc acc ttcaac aag ctc 2304 Leu Glu Met Ser Ser Leu Pro Asp Leu Thr Pro Thr Phe AsnLys Leu 755 760 765 tgt ggc aac tcc agg cag atg gct tgc acc cca ata tcatgc cct ggt 2352 Cys Gly Asn Ser Arg Gln Met Ala Cys Thr Pro Ile Ser CysPro Gly 770 775 780 gag cta tgt ccc caa gac aat ggc aca gcc tgt gcg tcccgc tgc agg 2400 Glu Leu Cys Pro Gln Asp Asn Gly Thr Ala Cys Ala Ser ArgCys Arg 785 790 795 800 ggt gtc ctt ccc agg gcc ggt ggg gcc ttc ttg atggcg ggg cag gtg 2448 Gly Val Leu Pro Arg Ala Gly Gly Ala Phe Leu Met AlaGly Gln Val 805 810 815 gct gag cag ctg cgg ggc ttc aat gcc cag ctc cagcgg acc agg cag 2496 Ala Glu Gln Leu Arg Gly Phe Asn Ala Gln Leu Gln ArgThr Arg Gln 820 825 830 atg att agg gca gcc gag gaa tct gcc tca cag attcaa tcc agt gcc 2544 Met Ile Arg Ala Ala Glu Glu Ser Ala Ser Gln Ile GlnSer Ser Ala 835 840 845 cag cgc ttg gag acc cag gtg agc gcc agc cgc tcccag atg gag gaa 2592 Gln Arg Leu Glu Thr Gln Val Ser Ala Ser Arg Ser GlnMet Glu Glu 850 855 860 gat gtc aga cgc aca cgg ctc cta atc cag cag gtccgg gac ttc cta 2640 Asp Val Arg Arg Thr Arg Leu Leu Ile Gln Gln Val ArgAsp Phe Leu 865 870 875 880 aca gac ccc gac act gat gca gcc act atc caggag gtc agc gag gcc 2688 Thr Asp Pro Asp Thr Asp Ala Ala Thr Ile Gln GluVal Ser Glu Ala 885 890 895 gtg ctg gcc ctg tgg ctg ccc aca gac tca gctact gtt ctg cag aag 2736 Val Leu Ala Leu Trp Leu Pro Thr Asp Ser Ala ThrVal Leu Gln Lys 900 905 910 atg aat gag atc cag gcc att gca gcc agg ctcccc aac gtg gac ttg 2784 Met Asn Glu Ile Gln Ala Ile Ala Ala Arg Leu ProAsn Val Asp Leu 915 920 925 gtg ctg tcc cag acc aag cag gac att gcg cgtgcc cgc cgg ttg cag 2832 Val Leu Ser Gln Thr Lys Gln Asp Ile Ala Arg AlaArg Arg Leu Gln 930 935 940 gct gag gct gag gaa gcc agg agc cga gcc catgca gtg gag ggc cag 2880 Ala Glu Ala Glu Glu Ala Arg Ser Arg Ala His AlaVal Glu Gly Gln 945 950 955 960 gtg gag gat gtg gtt ggg aac ctg cgg cagggg aca gtg gca ctg cag 2928 Val Glu Asp Val Val Gly Asn Leu Arg Gln GlyThr Val Ala Leu Gln 965 970 975 gaa gct cag gac acc atg caa ggc acc agccgg tcc ctt cgg ctt atc 2976 Glu Ala Gln Asp Thr Met Gln Gly Thr Ser ArgSer Leu Arg Leu Ile 980 985 990 cag gac agg gtt gct gag gtt cag cag gtactg cgg cca gca gaa aag 3024 Gln Asp Arg Val Ala Glu Val Gln Gln Val LeuArg Pro Ala Glu Lys 995 1000 1005 ctg gtg aca agc atg acc aag cag ctgggt gac ttc tgg aca cgg atg 3072 Leu Val Thr Ser Met Thr Lys Gln Leu GlyAsp Phe Trp Thr Arg Met 1010 1015 1020 gag gag ctc cgc cac caa gcc cggcag cag ggg gca gag gca gtc cag 3120 Glu Glu Leu Arg His Gln Ala Arg GlnGln Gly Ala Glu Ala Val Gln 1025 1030 1035 1040 gcc cag cag ctt gcg gaaggt gcc agc gag cag gca ttg agt gcc caa 3168 Ala Gln Gln Leu Ala Glu GlyAla Ser Glu Gln Ala Leu Ser Ala Gln 1045 1050 1055 gag gga ttt gag agaata aaa caa aag tat gct gag ttg aag gac cgg 3216 Glu Gly Phe Glu Arg IleLys Gln Lys Tyr Ala Glu Leu Lys Asp Arg 1060 1065 1070 ttg ggt cag agttcc atg ctg ggt gag cag ggt gcc cgg atc cag agt 3264 Leu Gly Gln Ser SerMet Leu Gly Glu Gln Gly Ala Arg Ile Gln Ser 1075 1080 1085 gtg aag acagag gca gag gag ctg ttt ggg gag acc atg gag atg atg 3312 Val Lys Thr GluAla Glu Glu Leu Phe Gly Glu Thr Met Glu Met Met 1090 1095 1100 gac aggatg aaa gac atg gag ttg gag ctg ctg cgg ggc agc cag gcc 3360 Asp Arg MetLys Asp Met Glu Leu Glu Leu Leu Arg Gly Ser Gln Ala 1105 1110 1115 1120atc atg ctg cgc tca gcg gac ctg aca gga ctg gag aag cgt gtg gag 3408 IleMet Leu Arg Ser Ala Asp Leu Thr Gly Leu Glu Lys Arg Val Glu 1125 11301135 cag atc cgt gac cac atc aat ggg cgc gtg ctc tac tat gcc acc tgc3456 Gln Ile Arg Asp His Ile Asn Gly Arg Val Leu Tyr Tyr Ala Thr Cys1140 1145 1150 aag tgatgctaca cgttccagcc cgttgcccca ctcatctgcgcgctttgctt 3509 Lys ttggttgggg ggcagattgg gttggaatgc tttccatctccaggagactt tcatgtagcc 3569 caaagtacag cctggaccac ccctggtgtg tgtagctagtaagattaccc tgagctgcag 3629 ctgagcctga gccaatggga cagttacact tgacagacaaagatggtgga gattggcatg 3689 ccattgaaac taagagctct caagtcaagg aagctgggctgggcagtatc ccccgccttt 3749 agttctccac 3759 16 1153 PRT Homo sapiens 16Gln Gln Ala Cys Ser Arg Gly Ala Cys Tyr Pro Pro Val Gly Asp Leu 1 5 1015 Leu Val Gly Arg Thr Arg Phe Leu Arg Ala Ser Ser Thr Cys Gly Leu 20 2530 Thr Lys Pro Glu Thr Tyr Cys Thr Gln Tyr Gly Glu Trp Gln Met Lys 35 4045 Cys Cys Lys Cys Asp Ser Arg Gln Pro His Asn Tyr Tyr Ser His Arg 50 5560 Val Glu Asn Val Ala Ser Ser Ser Gly Pro Met Arg Trp Trp Gln Ser 65 7075 80 Gln Asn Asp Val Asn Pro Val Ser Leu Gln Leu Asp Leu Asp Arg Arg 8590 95 Phe Gln Leu Gln Glu Val Met Met Glu Phe Arg Gly Pro Met Pro Ala100 105 110 Gly Met Leu Ile Glu Arg Ser Ser Asp Phe Gly Lys Thr Trp ArgVal 115 120 125 Tyr Gln Tyr Leu Ala Ala Asp Cys Thr Ser Thr Phe Pro ArgVal Arg 130 135 140 Gln Gly Arg Pro Gln Ser Trp Gln Asp Val Arg Cys GlnSer Leu Pro 145 150 155 160 Gln Arg Pro Asn Ala Arg Leu Asn Gly Gly LysVal Gln Leu Asn Leu 165 170 175 Met Asp Leu Val Ser Gly Ile Pro Ala ThrGln Ser Gln Lys Ile Gln 180 185 190 Glu Val Gly Glu Ile Thr Asn Leu ArgVal Asn Phe Thr Arg Leu Ala 195 200 205 Pro Val Pro Gln Arg Gly Tyr HisPro Pro Ser Ala Tyr Tyr Ala Val 210 215 220 Ser Gln Leu Arg Leu Gln GlySer Cys Phe Cys His Gly His Ala Asp 225 230 235 240 Arg Cys Ala Pro LysPro Gly Ala Ser Ala Gly Ser Thr Ala Val Gln 245 250 255 Val His Asp ValCys Val Cys Gln His Asn Thr Ala Gly Pro Asn Cys 260 265 270 Glu Arg CysAla Pro Phe Tyr Asn Asn Arg Pro Trp Arg Pro Ala Glu 275 280 285 Gly GlnAsp Ala His Glu Cys Gln Arg Cys Asp Cys Asn Gly His Ser 290 295 300 GluThr Cys His Phe Asp Pro Ala Val Phe Ala Ala Ser Gln Gly Ala 305 310 315320 Tyr Gly Gly Val Cys Asp Asn Cys Arg Asp His Thr Glu Gly Lys Asn 325330 335 Cys Glu Arg Cys Gln Leu His Tyr Phe Arg Asn Arg Arg Pro Gly Ala340 345 350 Ser Ile Gln Glu Thr Cys Ile Ser Cys Glu Cys Asp Pro Asp GlyAla 355 360 365 Val Ala Gly Ala Pro Cys Asp Pro Val Thr Gly Gln Cys ValCys Lys 370 375 380 Glu His Val Gln Gly Glu Arg Cys Asp Leu Cys Lys ProGly Phe Thr 385 390 395 400 Gly Leu Thr Tyr Ala Asn Pro Arg Arg Cys HisArg Cys Asp Cys Asn 405 410 415 Ile Leu Gly Ser Arg Glu Met Pro Cys AspGlu Glu Ser Gly Arg Cys 420 425 430 Leu Cys Leu Pro Asn Val Val Gly ProLys Cys Asp Gln Cys Ala Pro 435 440 445 Tyr His Trp Lys Leu Ala Ser GlyGln Gly Cys Glu Pro Cys Ala Cys 450 455 460 Asp Pro His Asn Ser Leu SerPro Gln Cys Asn Gln Phe Thr Gly Gln 465 470 475 480 Cys Pro Cys Arg GluGly Phe Gly Gly Leu Met Cys Ser Ala Ala Ala 485 490 495 Ile Arg Gln CysPro Asp Arg Thr Tyr Gly Asp Val Ala Thr Gly Cys 500 505 510 Arg Ala CysAsp Cys Asp Phe Arg Gly Thr Glu Gly Pro Gly Cys Asp 515 520 525 Lys AlaSer Gly Arg Cys Leu Cys Arg Pro Gly Leu Thr Gly Pro Arg 530 535 540 CysAsp Gln Cys Gln Arg Gly Tyr Cys Asn Arg Tyr Pro Val Cys Val 545 550 555560 Ala Cys His Pro Cys Phe Gln Thr Tyr Asp Ala Asp Leu Arg Glu Gln 565570 575 Ala Leu Arg Phe Gly Arg Leu Pro Asn Ala Thr Ala Ser Leu Trp Ser580 585 590 Gly Pro Gly Leu Glu Asp Arg Gly Leu Ala Ser Arg Ile Leu AspAla 595 600 605 Lys Ser Lys Ile Glu Gln Ile Arg Ala Val Leu Ser Ser ProAla Val 610 615 620 Thr Glu Gln Glu Val Ala Gln Val Ala Ser Ala Ile LeuSer Leu Arg 625 630 635 640 Arg Thr Leu Gln Gly Leu Gln Leu Asp Leu ProLeu Glu Glu Glu Thr 645 650 655 Leu Ser Leu Pro Arg Asp Leu Glu Ser LeuAsp Arg Ser Phe Asn Gly 660 665 670 Leu Leu Thr Met Tyr Gln Arg Lys ArgGlu Gln Phe Glu Lys Ile Ser 675 680 685 Ser Ala Asp Pro Ser Gly Ala PheArg Met Leu Ser Thr Ala Tyr Glu 690 695 700 Gln Ser Ala Gln Ala Ala GlnGln Val Ser Asp Ser Ser Arg Leu Leu 705 710 715 720 Asp Gln Leu Arg AspSer Arg Arg Glu Ala Glu Arg Leu Val Arg Gln 725 730 735 Ala Gly Gly GlyGly Gly Thr Gly Ser Pro Lys Leu Val Ala Leu Arg 740 745 750 Leu Glu MetSer Ser Leu Pro Asp Leu Thr Pro Thr Phe Asn Lys Leu 755 760 765 Cys GlyAsn Ser Arg Gln Met Ala Cys Thr Pro Ile Ser Cys Pro Gly 770 775 780 GluLeu Cys Pro Gln Asp Asn Gly Thr Ala Cys Ala Ser Arg Cys Arg 785 790 795800 Gly Val Leu Pro Arg Ala Gly Gly Ala Phe Leu Met Ala Gly Gln Val 805810 815 Ala Glu Gln Leu Arg Gly Phe Asn Ala Gln Leu Gln Arg Thr Arg Gln820 825 830 Met Ile Arg Ala Ala Glu Glu Ser Ala Ser Gln Ile Gln Ser SerAla 835 840 845 Gln Arg Leu Glu Thr Gln Val Ser Ala Ser Arg Ser Gln MetGlu Glu 850 855 860 Asp Val Arg Arg Thr Arg Leu Leu Ile Gln Gln Val ArgAsp Phe Leu 865 870 875 880 Thr Asp Pro Asp Thr Asp Ala Ala Thr Ile GlnGlu Val Ser Glu Ala 885 890 895 Val Leu Ala Leu Trp Leu Pro Thr Asp SerAla Thr Val Leu Gln Lys 900 905 910 Met Asn Glu Ile Gln Ala Ile Ala AlaArg Leu Pro Asn Val Asp Leu 915 920 925 Val Leu Ser Gln Thr Lys Gln AspIle Ala Arg Ala Arg Arg Leu Gln 930 935 940 Ala Glu Ala Glu Glu Ala ArgSer Arg Ala His Ala Val Glu Gly Gln 945 950 955 960 Val Glu Asp Val ValGly Asn Leu Arg Gln Gly Thr Val Ala Leu Gln 965 970 975 Glu Ala Gln AspThr Met Gln Gly Thr Ser Arg Ser Leu Arg Leu Ile 980 985 990 Gln Asp ArgVal Ala Glu Val Gln Gln Val Leu Arg Pro Ala Glu Lys 995 1000 1005 LeuVal Thr Ser Met Thr Lys Gln Leu Gly Asp Phe Trp Thr Arg Met 1010 10151020 Glu Glu Leu Arg His Gln Ala Arg Gln Gln Gly Ala Glu Ala Val Gln1025 1030 1035 1040 Ala Gln Gln Leu Ala Glu Gly Ala Ser Glu Gln Ala LeuSer Ala Gln 1045 1050 1055 Glu Gly Phe Glu Arg Ile Lys Gln Lys Tyr AlaGlu Leu Lys Asp Arg 1060 1065 1070 Leu Gly Gln Ser Ser Met Leu Gly GluGln Gly Ala Arg Ile Gln Ser 1075 1080 1085 Val Lys Thr Glu Ala Glu GluLeu Phe Gly Glu Thr Met Glu Met Met 1090 1095 1100 Asp Arg Met Lys AspMet Glu Leu Glu Leu Leu Arg Gly Ser Gln Ala 1105 1110 1115 1120 Ile MetLeu Arg Ser Ala Asp Leu Thr Gly Leu Glu Lys Arg Val Glu 1125 1130 1135Gln Ile Arg Asp His Ile Asn Gly Arg Val Leu Tyr Tyr Ala Thr Cys 11401145 1150 Lys 17 3621 DNA Homo sapiens CDS (60)..(3617) sig_peptide(60)..(110) misc_feature (123)..(146) 17 gtttaaactt aagcttctgcctgccgcctg cctgcctgcc actgagggtt cccagcacc 59 atg agg gcc tgg atc ttcttt ctc ctt tgc ctg gcc ggg agg gct ctg 107 Met Arg Ala Trp Ile Phe PheLeu Leu Cys Leu Ala Gly Arg Ala Leu 1 5 10 15 gca gcc cca cta gcc gactac aag gac gac gat gac aag cta gcc caa 155 Ala Ala Pro Leu Ala Asp TyrLys Asp Asp Asp Asp Lys Leu Ala Gln 20 25 30 caa gcc tgc tcc cgt ggg gcctgc tat cca cct gtt ggg gac ctg ctt 203 Gln Ala Cys Ser Arg Gly Ala CysTyr Pro Pro Val Gly Asp Leu Leu 35 40 45 gtt ggg agg acc cgg ttt ctc cgagct tca tct acc tgt gga ctg acc 251 Val Gly Arg Thr Arg Phe Leu Arg AlaSer Ser Thr Cys Gly Leu Thr 50 55 60 aag cct gag acc tac tgc acc cag tatggc gag tgg cag atg aaa tgc 299 Lys Pro Glu Thr Tyr Cys Thr Gln Tyr GlyGlu Trp Gln Met Lys Cys 65 70 75 80 tgc aag tgt gac tcc agg cag cct cacaac tac tac agt cac cga gta 347 Cys Lys Cys Asp Ser Arg Gln Pro His AsnTyr Tyr Ser His Arg Val 85 90 95 gag aat gtg gct tca tcc tcc ggc ccc atgcgc tgg tgg cag tcc cag 395 Glu Asn Val Ala Ser Ser Ser Gly Pro Met ArgTrp Trp Gln Ser Gln 100 105 110 aat gat gtg aac cct gtc tct ctg cag ctggac ctg gac agg aga ttc 443 Asn Asp Val Asn Pro Val Ser Leu Gln Leu AspLeu Asp Arg Arg Phe 115 120 125 cag ctt caa gaa gtc atg atg gag ttc cagggg ccc atg cct gcc ggc 491 Gln Leu Gln Glu Val Met Met Glu Phe Gln GlyPro Met Pro Ala Gly 130 135 140 atg ctg att gag cgc tcc tca gac ttc ggtaag acc tgg cga gtg tac 539 Met Leu Ile Glu Arg Ser Ser Asp Phe Gly LysThr Trp Arg Val Tyr 145 150 155 160 cag tac ctg gct gcc gac tgc acc tccacc ttc cct cgg gtc cgc cag 587 Gln Tyr Leu Ala Ala Asp Cys Thr Ser ThrPhe Pro Arg Val Arg Gln 165 170 175 ggt cgg cct cag agc tgg cag gat gttcgg tgc cag tcc ctg cct cag 635 Gly Arg Pro Gln Ser Trp Gln Asp Val ArgCys Gln Ser Leu Pro Gln 180 185 190 agg cct aat gca cgc cta aat ggg gggaag gtc caa ctt aac ctt atg 683 Arg Pro Asn Ala Arg Leu Asn Gly Gly LysVal Gln Leu Asn Leu Met 195 200 205 gat tta gtg tct ggg att cca gca actcaa agt caa aaa att caa gag 731 Asp Leu Val Ser Gly Ile Pro Ala Thr GlnSer Gln Lys Ile Gln Glu 210 215 220 gtg ggg gag atc aca aac ttg aga gtcaat ttc acc agg ctg gcc cct 779 Val Gly Glu Ile Thr Asn Leu Arg Val AsnPhe Thr Arg Leu Ala Pro 225 230 235 240 gtg ccc caa agg ggc tac cac cctccc agc gcc tac tat gct gtg tcc 827 Val Pro Gln Arg Gly Tyr His Pro ProSer Ala Tyr Tyr Ala Val Ser 245 250 255 cag ctc cgt ctg cag ggg agc tgcttc tgt cac ggc cat gct gat cgc 875 Gln Leu Arg Leu Gln Gly Ser Cys PheCys His Gly His Ala Asp Arg 260 265 270 tgc gca ccc aag cct ggg gcc tctgca ggc ccc tcc acc gct gtg cag 923 Cys Ala Pro Lys Pro Gly Ala Ser AlaGly Pro Ser Thr Ala Val Gln 275 280 285 gtc cac gat gtc tgc gtc tgc cagcac aac act gcc ggc cca aat tgt 971 Val His Asp Val Cys Val Cys Gln HisAsn Thr Ala Gly Pro Asn Cys 290 295 300 gag cgc tgt gca ccc ttc tac aacaac cgg ccc tgg aga ccg gcg gag 1019 Glu Arg Cys Ala Pro Phe Tyr Asn AsnArg Pro Trp Arg Pro Ala Glu 305 310 315 320 ggc cag gac gcc cat gaa tgccaa agg tgc gac tgc aat ggg cac tca 1067 Gly Gln Asp Ala His Glu Cys GlnArg Cys Asp Cys Asn Gly His Ser 325 330 335 gag aca tgt cac ttt gac cccgct gtg ttt gcc gcc agc cag ggg gca 1115 Glu Thr Cys His Phe Asp Pro AlaVal Phe Ala Ala Ser Gln Gly Ala 340 345 350 tat gga ggt gtg tgt gac aattgc cgg gac cac acc gaa ggc aag aac 1163 Tyr Gly Gly Val Cys Asp Asn CysArg Asp His Thr Glu Gly Lys Asn 355 360 365 tgt gag cgg tgt cag ctg cactat ttc cgg aac cgg cgc ccg gga gct 1211 Cys Glu Arg Cys Gln Leu His TyrPhe Arg Asn Arg Arg Pro Gly Ala 370 375 380 tcc att cag gag acc tgc atctcc tgc gag tgt gat ccg gat ggg gca 1259 Ser Ile Gln Glu Thr Cys Ile SerCys Glu Cys Asp Pro Asp Gly Ala 385 390 395 400 gtg cca ggg gct ccc tgtgac cca gtg acc ggg cag tgt gtg tgc aag 1307 Val Pro Gly Ala Pro Cys AspPro Val Thr Gly Gln Cys Val Cys Lys 405 410 415 gag cat gtg cag gga gagcgc tgt gac cta tgc aag ccg ggc ttc act 1355 Glu His Val Gln Gly Glu ArgCys Asp Leu Cys Lys Pro Gly Phe Thr 420 425 430 gga ctc acc tac gcc aacccg cag ggc tgc cac cgc tgt gac tgc aac 1403 Gly Leu Thr Tyr Ala Asn ProGln Gly Cys His Arg Cys Asp Cys Asn 435 440 445 atc ctg ggg tcc cgg agggac atg ccg tgt gac gag gag agt ggg cgc 1451 Ile Leu Gly Ser Arg Arg AspMet Pro Cys Asp Glu Glu Ser Gly Arg 450 455 460 tgc ctt tgt ctg ccc aacgtg gtg ggt ccc aaa tgt gac cag tgt gct 1499 Cys Leu Cys Leu Pro Asn ValVal Gly Pro Lys Cys Asp Gln Cys Ala 465 470 475 480 ccc tac cac tgg aagctg gcc agt ggc cag ggc tgt gaa ccg tgt gcc 1547 Pro Tyr His Trp Lys LeuAla Ser Gly Gln Gly Cys Glu Pro Cys Ala 485 490 495 tgc gac ccg cac aactcc ctc agc cca cag tgc aac cag ttc aca ggg 1595 Cys Asp Pro His Asn SerLeu Ser Pro Gln Cys Asn Gln Phe Thr Gly 500 505 510 cag tgc ccc tgt cgggaa ggc ttt ggt ggc ctg atg tgc agc gct gca 1643 Gln Cys Pro Cys Arg GluGly Phe Gly Gly Leu Met Cys Ser Ala Ala 515 520 525 gcc atc cgc cag tgtcca gac cgg acc tat gga gac gtg gcc aca gga 1691 Ala Ile Arg Gln Cys ProAsp Arg Thr Tyr Gly Asp Val Ala Thr Gly 530 535 540 tgc cga gcc tgt gactgt gat ttc cgg gga aca gag ggc ccg ggc tgc 1739 Cys Arg Ala Cys Asp CysAsp Phe Arg Gly Thr Glu Gly Pro Gly Cys 545 550 555 560 gac aag gca tcaggc cgc tgc ctc tgc cgc cct ggc ttg acc ggg ccc 1787 Asp Lys Ala Ser GlyArg Cys Leu Cys Arg Pro Gly Leu Thr Gly Pro 565 570 575 cgc tgt gac cagtgc cag cga ggc tac tgc aat cgc tac ccg gtg tgc 1835 Arg Cys Asp Gln CysGln Arg Gly Tyr Cys Asn Arg Tyr Pro Val Cys 580 585 590 gtg gcc tgc caccct tgc ttc cag acc tat gat gcg gac ctc cgg gag 1883 Val Ala Cys His ProCys Phe Gln Thr Tyr Asp Ala Asp Leu Arg Glu 595 600 605 cag gcc ctg cgcttt ggt aga ctc cgg aat gcc acc gcc agc ctg tgg 1931 Gln Ala Leu Arg PheGly Arg Leu Arg Asn Ala Thr Ala Ser Leu Trp 610 615 620 tca ggg cct gggctg gag gac cgt ggc ctg gcc tcc cgg atc cta gat 1979 Ser Gly Pro Gly LeuGlu Asp Arg Gly Leu Ala Ser Arg Ile Leu Asp 625 630 635 640 gca aag agtaag att gag cag atc cga gca gtt ctc agc agc ccc gca 2027 Ala Lys Ser LysIle Glu Gln Ile Arg Ala Val Leu Ser Ser Pro Ala 645 650 655 gtc aca gagcag gag gtg gct cag gtg gcc agt gcc atc ctc tcc ctc 2075 Val Thr Glu GlnGlu Val Ala Gln Val Ala Ser Ala Ile Leu Ser Leu 660 665 670 agg cga actctc cag ggc ctg cag ctg gat ctg ccc ctg gag gag gag 2123 Arg Arg Thr LeuGln Gly Leu Gln Leu Asp Leu Pro Leu Glu Glu Glu 675 680 685 acg ttg tccctt ccg aga gac ctg gag agt ctt gac aga agc ttc aat 2171 Thr Leu Ser LeuPro Arg Asp Leu Glu Ser Leu Asp Arg Ser Phe Asn 690 695 700 ggt ctc cttact atg tat cag agg aag agg gag cag ttt gaa aaa ata 2219 Gly Leu Leu ThrMet Tyr Gln Arg Lys Arg Glu Gln Phe Glu Lys Ile 705 710 715 720 agc agtgct gat cct tca gga gcc ttc cgg atg ctg agc aca gcc tac 2267 Ser Ser AlaAsp Pro Ser Gly Ala Phe Arg Met Leu Ser Thr Ala Tyr 725 730 735 gag cagtca gcc cag gct gct cag cag gtc tcc gac agc tcg cgc ctt 2315 Glu Gln SerAla Gln Ala Ala Gln Gln Val Ser Asp Ser Ser Arg Leu 740 745 750 ttg gaccag ctc agg gac agc cgg aga gag gca gag agg ctg gtg cgg 2363 Leu Asp GlnLeu Arg Asp Ser Arg Arg Glu Ala Glu Arg Leu Val Arg 755 760 765 cag gcggga gga gga gga ggc acc ggc agc ccc aag ctt gtg gcc ctg 2411 Gln Ala GlyGly Gly Gly Gly Thr Gly Ser Pro Lys Leu Val Ala Leu 770 775 780 agg ctggag atg tct tcg ttg cct gac ctg aca ccc acc ttc aac aag 2459 Arg Leu GluMet Ser Ser Leu Pro Asp Leu Thr Pro Thr Phe Asn Lys 785 790 795 800 ctctgt ggc aac tcc agg cag atg gct tgc acc cca ata tca tgc cct 2507 Leu CysGly Asn Ser Arg Gln Met Ala Cys Thr Pro Ile Ser Cys Pro 805 810 815 ggtgag cta tgt ccc caa gac aat ggc aca gcc tgt ggc tcc cgc tgc 2555 Gly GluLeu Cys Pro Gln Asp Asn Gly Thr Ala Cys Gly Ser Arg Cys 820 825 830 aggggt gtc ctt ccc agg gcc ggt ggg gcc ttc ttg atg gcg ggg cag 2603 Arg GlyVal Leu Pro Arg Ala Gly Gly Ala Phe Leu Met Ala Gly Gln 835 840 845 gtggct gag cag ctg cgg ggc ttc aat gcc cag ctc cag cgg acc agg 2651 Val AlaGlu Gln Leu Arg Gly Phe Asn Ala Gln Leu Gln Arg Thr Arg 850 855 860 cagatg att agg gca gcc gag gaa tct gcc tca cag att caa tcc agt 2699 Gln MetIle Arg Ala Ala Glu Glu Ser Ala Ser Gln Ile Gln Ser Ser 865 870 875 880gcc cag cgc ttg gag acc cag gtg agc gcc agc cgc tcc cag atg gag 2747 AlaGln Arg Leu Glu Thr Gln Val Ser Ala Ser Arg Ser Gln Met Glu 885 890 895gaa gat gtc aga cgc aca cgg ctc cta atc cag cag gtc cgg gac ttc 2795 GluAsp Val Arg Arg Thr Arg Leu Leu Ile Gln Gln Val Arg Asp Phe 900 905 910cta aca gac ccc gac act gat gca gcc act atc cag gag gtc agc gag 2843 LeuThr Asp Pro Asp Thr Asp Ala Ala Thr Ile Gln Glu Val Ser Glu 915 920 925gcc gtg ctg gcc ctg tgg ctg ccc aca gac tca gct act gtt ctg cag 2891 AlaVal Leu Ala Leu Trp Leu Pro Thr Asp Ser Ala Thr Val Leu Gln 930 935 940aag atg aat gag atc cag gcc att gca gcc agg ctc ccc aac gtg gac 2939 LysMet Asn Glu Ile Gln Ala Ile Ala Ala Arg Leu Pro Asn Val Asp 945 950 955960 ttg gtg ctg tcc cag acc aag cag gac att gcg cgt gcc cgc cgg ttg 2987Leu Val Leu Ser Gln Thr Lys Gln Asp Ile Ala Arg Ala Arg Arg Leu 965 970975 cag gct gag gct gag gaa gcc agg agc cga gcc cat gca gtg gag ggc 3035Gln Ala Glu Ala Glu Glu Ala Arg Ser Arg Ala His Ala Val Glu Gly 980 985990 cag gtg gaa gat gtg gtt ggg aac ctg cgg cag ggg aca gtg gca ctg 3083Gln Val Glu Asp Val Val Gly Asn Leu Arg Gln Gly Thr Val Ala Leu 995 10001005 cag gaa gct cag gac acc atg caa ggc acc agc cgc tcc ctt cgg ctt3131 Gln Glu Ala Gln Asp Thr Met Gln Gly Thr Ser Arg Ser Leu Arg Leu1010 1015 1020 atc cag gac agg gtt gct gag gtt cag cag gta ctg cgg ccagca gaa 3179 Ile Gln Asp Arg Val Ala Glu Val Gln Gln Val Leu Arg Pro AlaGlu 1025 1030 1035 1040 aag ctg gtg aca agc atg acc aag cag ctg ggt gacttc tgg aca cgg 3227 Lys Leu Val Thr Ser Met Thr Lys Gln Leu Gly Asp PheTrp Thr Arg 1045 1050 1055 atg gag gag ctc cgc cac caa gcc cgg cag cagggg gca gag gca gtc 3275 Met Glu Glu Leu Arg His Gln Ala Arg Gln Gln GlyAla Glu Ala Val 1060 1065 1070 cag gcc cag cag ctt gcg gaa ggt gcc agcgag cag gca ttg agt gcc 3323 Gln Ala Gln Gln Leu Ala Glu Gly Ala Ser GluGln Ala Leu Ser Ala 1075 1080 1085 caa gag gga ttt gag aga ata aaa caaaag tat gct gag ttg aag gac 3371 Gln Glu Gly Phe Glu Arg Ile Lys Gln LysTyr Ala Glu Leu Lys Asp 1090 1095 1100 cgg ttg ggt cag agt tcc atg ctgggt gag cag ggt gcc cgg atc cag 3419 Arg Leu Gly Gln Ser Ser Met Leu GlyGlu Gln Gly Ala Arg Ile Gln 1105 1110 1115 1120 agt gtg aag aca gag gcagag gag ctg ttt ggg gag acc atg gag atg 3467 Ser Val Lys Thr Glu Ala GluGlu Leu Phe Gly Glu Thr Met Glu Met 1125 1130 1135 atg gac agg atg aaagac atg gag ttg gag ctg ctg cgg ggc agc cag 3515 Met Asp Arg Met Lys AspMet Glu Leu Glu Leu Leu Arg Gly Ser Gln 1140 1145 1150 gcc atc atg ctgcgc tca gcg gac ctg aca gga ctg gag aag cgt gtg 3563 Ala Ile Met Leu ArgSer Ala Asp Leu Thr Gly Leu Glu Lys Arg Val 1155 1160 1165 gag cag atccgt gac cac atc aat ggg cgc gtg ctc tac tat gcc acc 3611 Glu Gln Ile ArgAsp His Ile Asn Gly Arg Val Leu Tyr Tyr Ala Thr 1170 1175 1180 tgc aagtgat 3621 Cys Lys 1185 18 1186 PRT Homo sapiens 18 Met Arg Ala Trp IlePhe Phe Leu Leu Cys Leu Ala Gly Arg Ala Leu 1 5 10 15 Ala Ala Pro LeuAla Asp Tyr Lys Asp Asp Asp Asp Lys Leu Ala Gln 20 25 30 Gln Ala Cys SerArg Gly Ala Cys Tyr Pro Pro Val Gly Asp Leu Leu 35 40 45 Val Gly Arg ThrArg Phe Leu Arg Ala Ser Ser Thr Cys Gly Leu Thr 50 55 60 Lys Pro Glu ThrTyr Cys Thr Gln Tyr Gly Glu Trp Gln Met Lys Cys 65 70 75 80 Cys Lys CysAsp Ser Arg Gln Pro His Asn Tyr Tyr Ser His Arg Val 85 90 95 Glu Asn ValAla Ser Ser Ser Gly Pro Met Arg Trp Trp Gln Ser Gln 100 105 110 Asn AspVal Asn Pro Val Ser Leu Gln Leu Asp Leu Asp Arg Arg Phe 115 120 125 GlnLeu Gln Glu Val Met Met Glu Phe Gln Gly Pro Met Pro Ala Gly 130 135 140Met Leu Ile Glu Arg Ser Ser Asp Phe Gly Lys Thr Trp Arg Val Tyr 145 150155 160 Gln Tyr Leu Ala Ala Asp Cys Thr Ser Thr Phe Pro Arg Val Arg Gln165 170 175 Gly Arg Pro Gln Ser Trp Gln Asp Val Arg Cys Gln Ser Leu ProGln 180 185 190 Arg Pro Asn Ala Arg Leu Asn Gly Gly Lys Val Gln Leu AsnLeu Met 195 200 205 Asp Leu Val Ser Gly Ile Pro Ala Thr Gln Ser Gln LysIle Gln Glu 210 215 220 Val Gly Glu Ile Thr Asn Leu Arg Val Asn Phe ThrArg Leu Ala Pro 225 230 235 240 Val Pro Gln Arg Gly Tyr His Pro Pro SerAla Tyr Tyr Ala Val Ser 245 250 255 Gln Leu Arg Leu Gln Gly Ser Cys PheCys His Gly His Ala Asp Arg 260 265 270 Cys Ala Pro Lys Pro Gly Ala SerAla Gly Pro Ser Thr Ala Val Gln 275 280 285 Val His Asp Val Cys Val CysGln His Asn Thr Ala Gly Pro Asn Cys 290 295 300 Glu Arg Cys Ala Pro PheTyr Asn Asn Arg Pro Trp Arg Pro Ala Glu 305 310 315 320 Gly Gln Asp AlaHis Glu Cys Gln Arg Cys Asp Cys Asn Gly His Ser 325 330 335 Glu Thr CysHis Phe Asp Pro Ala Val Phe Ala Ala Ser Gln Gly Ala 340 345 350 Tyr GlyGly Val Cys Asp Asn Cys Arg Asp His Thr Glu Gly Lys Asn 355 360 365 CysGlu Arg Cys Gln Leu His Tyr Phe Arg Asn Arg Arg Pro Gly Ala 370 375 380Ser Ile Gln Glu Thr Cys Ile Ser Cys Glu Cys Asp Pro Asp Gly Ala 385 390395 400 Val Pro Gly Ala Pro Cys Asp Pro Val Thr Gly Gln Cys Val Cys Lys405 410 415 Glu His Val Gln Gly Glu Arg Cys Asp Leu Cys Lys Pro Gly PheThr 420 425 430 Gly Leu Thr Tyr Ala Asn Pro Gln Gly Cys His Arg Cys AspCys Asn 435 440 445 Ile Leu Gly Ser Arg Arg Asp Met Pro Cys Asp Glu GluSer Gly Arg 450 455 460 Cys Leu Cys Leu Pro Asn Val Val Gly Pro Lys CysAsp Gln Cys Ala 465 470 475 480 Pro Tyr His Trp Lys Leu Ala Ser Gly GlnGly Cys Glu Pro Cys Ala 485 490 495 Cys Asp Pro His Asn Ser Leu Ser ProGln Cys Asn Gln Phe Thr Gly 500 505 510 Gln Cys Pro Cys Arg Glu Gly PheGly Gly Leu Met Cys Ser Ala Ala 515 520 525 Ala Ile Arg Gln Cys Pro AspArg Thr Tyr Gly Asp Val Ala Thr Gly 530 535 540 Cys Arg Ala Cys Asp CysAsp Phe Arg Gly Thr Glu Gly Pro Gly Cys 545 550 555 560 Asp Lys Ala SerGly Arg Cys Leu Cys Arg Pro Gly Leu Thr Gly Pro 565 570 575 Arg Cys AspGln Cys Gln Arg Gly Tyr Cys Asn Arg Tyr Pro Val Cys 580 585 590 Val AlaCys His Pro Cys Phe Gln Thr Tyr Asp Ala Asp Leu Arg Glu 595 600 605 GlnAla Leu Arg Phe Gly Arg Leu Arg Asn Ala Thr Ala Ser Leu Trp 610 615 620Ser Gly Pro Gly Leu Glu Asp Arg Gly Leu Ala Ser Arg Ile Leu Asp 625 630635 640 Ala Lys Ser Lys Ile Glu Gln Ile Arg Ala Val Leu Ser Ser Pro Ala645 650 655 Val Thr Glu Gln Glu Val Ala Gln Val Ala Ser Ala Ile Leu SerLeu 660 665 670 Arg Arg Thr Leu Gln Gly Leu Gln Leu Asp Leu Pro Leu GluGlu Glu 675 680 685 Thr Leu Ser Leu Pro Arg Asp Leu Glu Ser Leu Asp ArgSer Phe Asn 690 695 700 Gly Leu Leu Thr Met Tyr Gln Arg Lys Arg Glu GlnPhe Glu Lys Ile 705 710 715 720 Ser Ser Ala Asp Pro Ser Gly Ala Phe ArgMet Leu Ser Thr Ala Tyr 725 730 735 Glu Gln Ser Ala Gln Ala Ala Gln GlnVal Ser Asp Ser Ser Arg Leu 740 745 750 Leu Asp Gln Leu Arg Asp Ser ArgArg Glu Ala Glu Arg Leu Val Arg 755 760 765 Gln Ala Gly Gly Gly Gly GlyThr Gly Ser Pro Lys Leu Val Ala Leu 770 775 780 Arg Leu Glu Met Ser SerLeu Pro Asp Leu Thr Pro Thr Phe Asn Lys 785 790 795 800 Leu Cys Gly AsnSer Arg Gln Met Ala Cys Thr Pro Ile Ser Cys Pro 805 810 815 Gly Glu LeuCys Pro Gln Asp Asn Gly Thr Ala Cys Gly Ser Arg Cys 820 825 830 Arg GlyVal Leu Pro Arg Ala Gly Gly Ala Phe Leu Met Ala Gly Gln 835 840 845 ValAla Glu Gln Leu Arg Gly Phe Asn Ala Gln Leu Gln Arg Thr Arg 850 855 860Gln Met Ile Arg Ala Ala Glu Glu Ser Ala Ser Gln Ile Gln Ser Ser 865 870875 880 Ala Gln Arg Leu Glu Thr Gln Val Ser Ala Ser Arg Ser Gln Met Glu885 890 895 Glu Asp Val Arg Arg Thr Arg Leu Leu Ile Gln Gln Val Arg AspPhe 900 905 910 Leu Thr Asp Pro Asp Thr Asp Ala Ala Thr Ile Gln Glu ValSer Glu 915 920 925 Ala Val Leu Ala Leu Trp Leu Pro Thr Asp Ser Ala ThrVal Leu Gln 930 935 940 Lys Met Asn Glu Ile Gln Ala Ile Ala Ala Arg LeuPro Asn Val Asp 945 950 955 960 Leu Val Leu Ser Gln Thr Lys Gln Asp IleAla Arg Ala Arg Arg Leu 965 970 975 Gln Ala Glu Ala Glu Glu Ala Arg SerArg Ala His Ala Val Glu Gly 980 985 990 Gln Val Glu Asp Val Val Gly AsnLeu Arg Gln Gly Thr Val Ala Leu 995 1000 1005 Gln Glu Ala Gln Asp ThrMet Gln Gly Thr Ser Arg Ser Leu Arg Leu 1010 1015 1020 Ile Gln Asp ArgVal Ala Glu Val Gln Gln Val Leu Arg Pro Ala Glu 1025 1030 1035 1040 LysLeu Val Thr Ser Met Thr Lys Gln Leu Gly Asp Phe Trp Thr Arg 1045 10501055 Met Glu Glu Leu Arg His Gln Ala Arg Gln Gln Gly Ala Glu Ala Val1060 1065 1070 Gln Ala Gln Gln Leu Ala Glu Gly Ala Ser Glu Gln Ala LeuSer Ala 1075 1080 1085 Gln Glu Gly Phe Glu Arg Ile Lys Gln Lys Tyr AlaGlu Leu Lys Asp 1090 1095 1100 Arg Leu Gly Gln Ser Ser Met Leu Gly GluGln Gly Ala Arg Ile Gln 1105 1110 1115 1120 Ser Val Lys Thr Glu Ala GluGlu Leu Phe Gly Glu Thr Met Glu Met 1125 1130 1135 Met Asp Arg Met LysAsp Met Glu Leu Glu Leu Leu Arg Gly Ser Gln 1140 1145 1150 Ala Ile MetLeu Arg Ser Ala Asp Leu Thr Gly Leu Glu Lys Arg Val 1155 1160 1165 GluGln Ile Arg Asp His Ile Asn Gly Arg Val Leu Tyr Tyr Ala Thr 1170 11751180 Cys Lys 1185 19 3511 DNA Homo sapiens CDS (7)..(3507) misc_feature(13)..(36) 19 gcccca cta gcc gac tac aag gac gac gat gac aag cta gcc caacaa 48 Leu Ala Asp Tyr Lys Asp Asp Asp Asp Lys Leu Ala Gln Gln 1 5 10gcc tgc tcc cgt ggg gcc tgc tat cca cct gtt ggg gac ctg ctt gtt 96 AlaCys Ser Arg Gly Ala Cys Tyr Pro Pro Val Gly Asp Leu Leu Val 15 20 25 30ggg agg acc cgg ttt ctc cga gct tca tct acc tgt gga ctg acc aag 144 GlyArg Thr Arg Phe Leu Arg Ala Ser Ser Thr Cys Gly Leu Thr Lys 35 40 45 cctgag acc tac tgc acc cag tat ggc gag tgg cag atg aaa tgc tgc 192 Pro GluThr Tyr Cys Thr Gln Tyr Gly Glu Trp Gln Met Lys Cys Cys 50 55 60 aag tgtgac tcc agg cag cct cac aac tac tac agt cac cga gta gag 240 Lys Cys AspSer Arg Gln Pro His Asn Tyr Tyr Ser His Arg Val Glu 65 70 75 aat gtg gcttca tcc tcc ggc ccc atg cgc tgg tgg cag tcc cag aat 288 Asn Val Ala SerSer Ser Gly Pro Met Arg Trp Trp Gln Ser Gln Asn 80 85 90 gat gtg aac cctgtc tct ctg cag ctg gac ctg gac agg aga ttc cag 336 Asp Val Asn Pro ValSer Leu Gln Leu Asp Leu Asp Arg Arg Phe Gln 95 100 105 110 ctt caa gaagtc atg atg gag ttc cag ggg ccc atg cct gcc ggc atg 384 Leu Gln Glu ValMet Met Glu Phe Gln Gly Pro Met Pro Ala Gly Met 115 120 125 ctg att gagcgc tcc tca gac ttc ggt aag acc tgg cga gtg tac cag 432 Leu Ile Glu ArgSer Ser Asp Phe Gly Lys Thr Trp Arg Val Tyr Gln 130 135 140 tac ctg gctgcc gac tgc acc tcc acc ttc cct cgg gtc cgc cag ggt 480 Tyr Leu Ala AlaAsp Cys Thr Ser Thr Phe Pro Arg Val Arg Gln Gly 145 150 155 cgg cct cagagc tgg cag gat gtt cgg tgc cag tcc ctg cct cag agg 528 Arg Pro Gln SerTrp Gln Asp Val Arg Cys Gln Ser Leu Pro Gln Arg 160 165 170 cct aat gcacgc cta aat ggg ggg aag gtc caa ctt aac ctt atg gat 576 Pro Asn Ala ArgLeu Asn Gly Gly Lys Val Gln Leu Asn Leu Met Asp 175 180 185 190 tta gtgtct ggg att cca gca act caa agt caa aaa att caa gag gtg 624 Leu Val SerGly Ile Pro Ala Thr Gln Ser Gln Lys Ile Gln Glu Val 195 200 205 ggg gagatc aca aac ttg aga gtc aat ttc acc agg ctg gcc cct gtg 672 Gly Glu IleThr Asn Leu Arg Val Asn Phe Thr Arg Leu Ala Pro Val 210 215 220 ccc caaagg ggc tac cac cct ccc agc gcc tac tat gct gtg tcc cag 720 Pro Gln ArgGly Tyr His Pro Pro Ser Ala Tyr Tyr Ala Val Ser Gln 225 230 235 ctc cgtctg cag ggg agc tgc ttc tgt cac ggc cat gct gat cgc tgc 768 Leu Arg LeuGln Gly Ser Cys Phe Cys His Gly His Ala Asp Arg Cys 240 245 250 gca cccaag cct ggg gcc tct gca ggc ccc tcc acc gct gtg cag gtc 816 Ala Pro LysPro Gly Ala Ser Ala Gly Pro Ser Thr Ala Val Gln Val 255 260 265 270 cacgat gtc tgc gtc tgc cag cac aac act gcc ggc cca aat tgt gag 864 His AspVal Cys Val Cys Gln His Asn Thr Ala Gly Pro Asn Cys Glu 275 280 285 cgctgt gca ccc ttc tac aac aac cgg ccc tgg aga ccg gcg gag ggc 912 Arg CysAla Pro Phe Tyr Asn Asn Arg Pro Trp Arg Pro Ala Glu Gly 290 295 300 caggac gcc cat gaa tgc caa agg tgc gac tgc aat ggg cac tca gag 960 Gln AspAla His Glu Cys Gln Arg Cys Asp Cys Asn Gly His Ser Glu 305 310 315 acatgt cac ttt gac ccc gct gtg ttt gcc gcc agc cag ggg gca tat 1008 Thr CysHis Phe Asp Pro Ala Val Phe Ala Ala Ser Gln Gly Ala Tyr 320 325 330 ggaggt gtg tgt gac aat tgc cgg gac cac acc gaa ggc aag aac tgt 1056 Gly GlyVal Cys Asp Asn Cys Arg Asp His Thr Glu Gly Lys Asn Cys 335 340 345 350gag cgg tgt cag ctg cac tat ttc cgg aac cgg cgc ccg gga gct tcc 1104 GluArg Cys Gln Leu His Tyr Phe Arg Asn Arg Arg Pro Gly Ala Ser 355 360 365att cag gag acc tgc atc tcc tgc gag tgt gat ccg gat ggg gca gtg 1152 IleGln Glu Thr Cys Ile Ser Cys Glu Cys Asp Pro Asp Gly Ala Val 370 375 380cca ggg gct ccc tgt gac cca gtg acc ggg cag tgt gtg tgc aag gag 1200 ProGly Ala Pro Cys Asp Pro Val Thr Gly Gln Cys Val Cys Lys Glu 385 390 395cat gtg cag gga gag cgc tgt gac cta tgc aag ccg ggc ttc act gga 1248 HisVal Gln Gly Glu Arg Cys Asp Leu Cys Lys Pro Gly Phe Thr Gly 400 405 410ctc acc tac gcc aac ccg cag ggc tgc cac cgc tgt gac tgc aac atc 1296 LeuThr Tyr Ala Asn Pro Gln Gly Cys His Arg Cys Asp Cys Asn Ile 415 420 425430 ctg ggg tcc cgg agg gac atg ccg tgt gac gag gag agt ggg cgc tgc 1344Leu Gly Ser Arg Arg Asp Met Pro Cys Asp Glu Glu Ser Gly Arg Cys 435 440445 ctt tgt ctg ccc aac gtg gtg ggt ccc aaa tgt gac cag tgt gct ccc 1392Leu Cys Leu Pro Asn Val Val Gly Pro Lys Cys Asp Gln Cys Ala Pro 450 455460 tac cac tgg aag ctg gcc agt ggc cag ggc tgt gaa ccg tgt gcc tgc 1440Tyr His Trp Lys Leu Ala Ser Gly Gln Gly Cys Glu Pro Cys Ala Cys 465 470475 gac ccg cac aac tcc ctc agc cca cag tgc aac cag ttc aca ggg cag 1488Asp Pro His Asn Ser Leu Ser Pro Gln Cys Asn Gln Phe Thr Gly Gln 480 485490 tgc ccc tgt cgg gaa ggc ttt ggt ggc ctg atg tgc agc gct gca gcc 1536Cys Pro Cys Arg Glu Gly Phe Gly Gly Leu Met Cys Ser Ala Ala Ala 495 500505 510 atc cgc cag tgt cca gac cgg acc tat gga gac gtg gcc aca gga tgc1584 Ile Arg Gln Cys Pro Asp Arg Thr Tyr Gly Asp Val Ala Thr Gly Cys 515520 525 cga gcc tgt gac tgt gat ttc cgg gga aca gag ggc ccg ggc tgc gac1632 Arg Ala Cys Asp Cys Asp Phe Arg Gly Thr Glu Gly Pro Gly Cys Asp 530535 540 aag gca tca ggc cgc tgc ctc tgc cgc cct ggc ttg acc ggg ccc cgc1680 Lys Ala Ser Gly Arg Cys Leu Cys Arg Pro Gly Leu Thr Gly Pro Arg 545550 555 tgt gac cag tgc cag cga ggc tac tgc aat cgc tac ccg gtg tgc gtg1728 Cys Asp Gln Cys Gln Arg Gly Tyr Cys Asn Arg Tyr Pro Val Cys Val 560565 570 gcc tgc cac cct tgc ttc cag acc tat gat gcg gac ctc cgg gag cag1776 Ala Cys His Pro Cys Phe Gln Thr Tyr Asp Ala Asp Leu Arg Glu Gln 575580 585 590 gcc ctg cgc ttt ggt aga ctc cgg aat gcc acc gcc agc ctg tggtca 1824 Ala Leu Arg Phe Gly Arg Leu Arg Asn Ala Thr Ala Ser Leu Trp Ser595 600 605 ggg cct ggg ctg gag gac cgt ggc ctg gcc tcc cgg atc cta gatgca 1872 Gly Pro Gly Leu Glu Asp Arg Gly Leu Ala Ser Arg Ile Leu Asp Ala610 615 620 aag agt aag att gag cag atc cga gca gtt ctc agc agc ccc gcagtc 1920 Lys Ser Lys Ile Glu Gln Ile Arg Ala Val Leu Ser Ser Pro Ala Val625 630 635 aca gag cag gag gtg gct cag gtg gcc agt gcc atc ctc tcc ctcagg 1968 Thr Glu Gln Glu Val Ala Gln Val Ala Ser Ala Ile Leu Ser Leu Arg640 645 650 cga act ctc cag ggc ctg cag ctg gat ctg ccc ctg gag gag gagacg 2016 Arg Thr Leu Gln Gly Leu Gln Leu Asp Leu Pro Leu Glu Glu Glu Thr655 660 665 670 ttg tcc ctt ccg aga gac ctg gag agt ctt gac aga agc ttcaat ggt 2064 Leu Ser Leu Pro Arg Asp Leu Glu Ser Leu Asp Arg Ser Phe AsnGly 675 680 685 ctc ctt act atg tat cag agg aag agg gag cag ttt gaa aaaata agc 2112 Leu Leu Thr Met Tyr Gln Arg Lys Arg Glu Gln Phe Glu Lys IleSer 690 695 700 agt gct gat cct tca gga gcc ttc cgg atg ctg agc aca gcctac gag 2160 Ser Ala Asp Pro Ser Gly Ala Phe Arg Met Leu Ser Thr Ala TyrGlu 705 710 715 cag tca gcc cag gct gct cag cag gtc tcc gac agc tcg cgcctt ttg 2208 Gln Ser Ala Gln Ala Ala Gln Gln Val Ser Asp Ser Ser Arg LeuLeu 720 725 730 gac cag ctc agg gac agc cgg aga gag gca gag agg ctg gtgcgg cag 2256 Asp Gln Leu Arg Asp Ser Arg Arg Glu Ala Glu Arg Leu Val ArgGln 735 740 745 750 gcg gga gga gga gga ggc acc ggc agc ccc aag ctt gtggcc ctg agg 2304 Ala Gly Gly Gly Gly Gly Thr Gly Ser Pro Lys Leu Val AlaLeu Arg 755 760 765 ctg gag atg tct tcg ttg cct gac ctg aca ccc acc ttcaac aag ctc 2352 Leu Glu Met Ser Ser Leu Pro Asp Leu Thr Pro Thr Phe AsnLys Leu 770 775 780 tgt ggc aac tcc agg cag atg gct tgc acc cca ata tcatgc cct ggt 2400 Cys Gly Asn Ser Arg Gln Met Ala Cys Thr Pro Ile Ser CysPro Gly 785 790 795 gag cta tgt ccc caa gac aat ggc aca gcc tgt ggc tcccgc tgc agg 2448 Glu Leu Cys Pro Gln Asp Asn Gly Thr Ala Cys Gly Ser ArgCys Arg 800 805 810 ggt gtc ctt ccc agg gcc ggt ggg gcc ttc ttg atg gcgggg cag gtg 2496 Gly Val Leu Pro Arg Ala Gly Gly Ala Phe Leu Met Ala GlyGln Val 815 820 825 830 gct gag cag ctg cgg ggc ttc aat gcc cag ctc cagcgg acc agg cag 2544 Ala Glu Gln Leu Arg Gly Phe Asn Ala Gln Leu Gln ArgThr Arg Gln 835 840 845 atg att agg gca gcc gag gaa tct gcc tca cag attcaa tcc agt gcc 2592 Met Ile Arg Ala Ala Glu Glu Ser Ala Ser Gln Ile GlnSer Ser Ala 850 855 860 cag cgc ttg gag acc cag gtg agc gcc agc cgc tcccag atg gag gaa 2640 Gln Arg Leu Glu Thr Gln Val Ser Ala Ser Arg Ser GlnMet Glu Glu 865 870 875 gat gtc aga cgc aca cgg ctc cta atc cag cag gtccgg gac ttc cta 2688 Asp Val Arg Arg Thr Arg Leu Leu Ile Gln Gln Val ArgAsp Phe Leu 880 885 890 aca gac ccc gac act gat gca gcc act atc cag gaggtc agc gag gcc 2736 Thr Asp Pro Asp Thr Asp Ala Ala Thr Ile Gln Glu ValSer Glu Ala 895 900 905 910 gtg ctg gcc ctg tgg ctg ccc aca gac tca gctact gtt ctg cag aag 2784 Val Leu Ala Leu Trp Leu Pro Thr Asp Ser Ala ThrVal Leu Gln Lys 915 920 925 atg aat gag atc cag gcc att gca gcc agg ctcccc aac gtg gac ttg 2832 Met Asn Glu Ile Gln Ala Ile Ala Ala Arg Leu ProAsn Val Asp Leu 930 935 940 gtg ctg tcc cag acc aag cag gac att gcg cgtgcc cgc cgg ttg cag 2880 Val Leu Ser Gln Thr Lys Gln Asp Ile Ala Arg AlaArg Arg Leu Gln 945 950 955 gct gag gct gag gaa gcc agg agc cga gcc catgca gtg gag ggc cag 2928 Ala Glu Ala Glu Glu Ala Arg Ser Arg Ala His AlaVal Glu Gly Gln 960 965 970 gtg gaa gat gtg gtt ggg aac ctg cgg cag gggaca gtg gca ctg cag 2976 Val Glu Asp Val Val Gly Asn Leu Arg Gln Gly ThrVal Ala Leu Gln 975 980 985 990 gaa gct cag gac acc atg caa ggc acc agccgc tcc ctt cgg ctt atc 3024 Glu Ala Gln Asp Thr Met Gln Gly Thr Ser ArgSer Leu Arg Leu Ile 995 1000 1005 cag gac agg gtt gct gag gtt cag caggta ctg cgg cca gca gaa aag 3072 Gln Asp Arg Val Ala Glu Val Gln Gln ValLeu Arg Pro Ala Glu Lys 1010 1015 1020 ctg gtg aca agc atg acc aag cagctg ggt gac ttc tgg aca cgg atg 3120 Leu Val Thr Ser Met Thr Lys Gln LeuGly Asp Phe Trp Thr Arg Met 1025 1030 1035 gag gag ctc cgc cac caa gcccgg cag cag ggg gca gag gca gtc cag 3168 Glu Glu Leu Arg His Gln Ala ArgGln Gln Gly Ala Glu Ala Val Gln 1040 1045 1050 gcc cag cag ctt gcg gaaggt gcc agc gag cag gca ttg agt gcc caa 3216 Ala Gln Gln Leu Ala Glu GlyAla Ser Glu Gln Ala Leu Ser Ala Gln 1055 1060 1065 1070 gag gga ttt gagaga ata aaa caa aag tat gct gag ttg aag gac cgg 3264 Glu Gly Phe Glu ArgIle Lys Gln Lys Tyr Ala Glu Leu Lys Asp Arg 1075 1080 1085 ttg ggt cagagt tcc atg ctg ggt gag cag ggt gcc cgg atc cag agt 3312 Leu Gly Gln SerSer Met Leu Gly Glu Gln Gly Ala Arg Ile Gln Ser 1090 1095 1100 gtg aagaca gag gca gag gag ctg ttt ggg gag acc atg gag atg atg 3360 Val Lys ThrGlu Ala Glu Glu Leu Phe Gly Glu Thr Met Glu Met Met 1105 1110 1115 gacagg atg aaa gac atg gag ttg gag ctg ctg cgg ggc agc cag gcc 3408 Asp ArgMet Lys Asp Met Glu Leu Glu Leu Leu Arg Gly Ser Gln Ala 1120 1125 1130atc atg ctg cgc tca gcg gac ctg aca gga ctg gag aag cgt gtg gag 3456 IleMet Leu Arg Ser Ala Asp Leu Thr Gly Leu Glu Lys Arg Val Glu 1135 11401145 1150 cag atc cgt gac cac atc aat ggg cgc gtg ctc tac tat gcc acctgc 3504 Gln Ile Arg Asp His Ile Asn Gly Arg Val Leu Tyr Tyr Ala Thr Cys1155 1160 1165 aag tgat 3511 Lys 20 1167 PRT Homo sapiens 20 Leu Ala AspTyr Lys Asp Asp Asp Asp Lys Leu Ala Gln Gln Ala Cys 1 5 10 15 Ser ArgGly Ala Cys Tyr Pro Pro Val Gly Asp Leu Leu Val Gly Arg 20 25 30 Thr ArgPhe Leu Arg Ala Ser Ser Thr Cys Gly Leu Thr Lys Pro Glu 35 40 45 Thr TyrCys Thr Gln Tyr Gly Glu Trp Gln Met Lys Cys Cys Lys Cys 50 55 60 Asp SerArg Gln Pro His Asn Tyr Tyr Ser His Arg Val Glu Asn Val 65 70 75 80 AlaSer Ser Ser Gly Pro Met Arg Trp Trp Gln Ser Gln Asn Asp Val 85 90 95 AsnPro Val Ser Leu Gln Leu Asp Leu Asp Arg Arg Phe Gln Leu Gln 100 105 110Glu Val Met Met Glu Phe Gln Gly Pro Met Pro Ala Gly Met Leu Ile 115 120125 Glu Arg Ser Ser Asp Phe Gly Lys Thr Trp Arg Val Tyr Gln Tyr Leu 130135 140 Ala Ala Asp Cys Thr Ser Thr Phe Pro Arg Val Arg Gln Gly Arg Pro145 150 155 160 Gln Ser Trp Gln Asp Val Arg Cys Gln Ser Leu Pro Gln ArgPro Asn 165 170 175 Ala Arg Leu Asn Gly Gly Lys Val Gln Leu Asn Leu MetAsp Leu Val 180 185 190 Ser Gly Ile Pro Ala Thr Gln Ser Gln Lys Ile GlnGlu Val Gly Glu 195 200 205 Ile Thr Asn Leu Arg Val Asn Phe Thr Arg LeuAla Pro Val Pro Gln 210 215 220 Arg Gly Tyr His Pro Pro Ser Ala Tyr TyrAla Val Ser Gln Leu Arg 225 230 235 240 Leu Gln Gly Ser Cys Phe Cys HisGly His Ala Asp Arg Cys Ala Pro 245 250 255 Lys Pro Gly Ala Ser Ala GlyPro Ser Thr Ala Val Gln Val His Asp 260 265 270 Val Cys Val Cys Gln HisAsn Thr Ala Gly Pro Asn Cys Glu Arg Cys 275 280 285 Ala Pro Phe Tyr AsnAsn Arg Pro Trp Arg Pro Ala Glu Gly Gln Asp 290 295 300 Ala His Glu CysGln Arg Cys Asp Cys Asn Gly His Ser Glu Thr Cys 305 310 315 320 His PheAsp Pro Ala Val Phe Ala Ala Ser Gln Gly Ala Tyr Gly Gly 325 330 335 ValCys Asp Asn Cys Arg Asp His Thr Glu Gly Lys Asn Cys Glu Arg 340 345 350Cys Gln Leu His Tyr Phe Arg Asn Arg Arg Pro Gly Ala Ser Ile Gln 355 360365 Glu Thr Cys Ile Ser Cys Glu Cys Asp Pro Asp Gly Ala Val Pro Gly 370375 380 Ala Pro Cys Asp Pro Val Thr Gly Gln Cys Val Cys Lys Glu His Val385 390 395 400 Gln Gly Glu Arg Cys Asp Leu Cys Lys Pro Gly Phe Thr GlyLeu Thr 405 410 415 Tyr Ala Asn Pro Gln Gly Cys His Arg Cys Asp Cys AsnIle Leu Gly 420 425 430 Ser Arg Arg Asp Met Pro Cys Asp Glu Glu Ser GlyArg Cys Leu Cys 435 440 445 Leu Pro Asn Val Val Gly Pro Lys Cys Asp GlnCys Ala Pro Tyr His 450 455 460 Trp Lys Leu Ala Ser Gly Gln Gly Cys GluPro Cys Ala Cys Asp Pro 465 470 475 480 His Asn Ser Leu Ser Pro Gln CysAsn Gln Phe Thr Gly Gln Cys Pro 485 490 495 Cys Arg Glu Gly Phe Gly GlyLeu Met Cys Ser Ala Ala Ala Ile Arg 500 505 510 Gln Cys Pro Asp Arg ThrTyr Gly Asp Val Ala Thr Gly Cys Arg Ala 515 520 525 Cys Asp Cys Asp PheArg Gly Thr Glu Gly Pro Gly Cys Asp Lys Ala 530 535 540 Ser Gly Arg CysLeu Cys Arg Pro Gly Leu Thr Gly Pro Arg Cys Asp 545 550 555 560 Gln CysGln Arg Gly Tyr Cys Asn Arg Tyr Pro Val Cys Val Ala Cys 565 570 575 HisPro Cys Phe Gln Thr Tyr Asp Ala Asp Leu Arg Glu Gln Ala Leu 580 585 590Arg Phe Gly Arg Leu Arg Asn Ala Thr Ala Ser Leu Trp Ser Gly Pro 595 600605 Gly Leu Glu Asp Arg Gly Leu Ala Ser Arg Ile Leu Asp Ala Lys Ser 610615 620 Lys Ile Glu Gln Ile Arg Ala Val Leu Ser Ser Pro Ala Val Thr Glu625 630 635 640 Gln Glu Val Ala Gln Val Ala Ser Ala Ile Leu Ser Leu ArgArg Thr 645 650 655 Leu Gln Gly Leu Gln Leu Asp Leu Pro Leu Glu Glu GluThr Leu Ser 660 665 670 Leu Pro Arg Asp Leu Glu Ser Leu Asp Arg Ser PheAsn Gly Leu Leu 675 680 685 Thr Met Tyr Gln Arg Lys Arg Glu Gln Phe GluLys Ile Ser Ser Ala 690 695 700 Asp Pro Ser Gly Ala Phe Arg Met Leu SerThr Ala Tyr Glu Gln Ser 705 710 715 720 Ala Gln Ala Ala Gln Gln Val SerAsp Ser Ser Arg Leu Leu Asp Gln 725 730 735 Leu Arg Asp Ser Arg Arg GluAla Glu Arg Leu Val Arg Gln Ala Gly 740 745 750 Gly Gly Gly Gly Thr GlySer Pro Lys Leu Val Ala Leu Arg Leu Glu 755 760 765 Met Ser Ser Leu ProAsp Leu Thr Pro Thr Phe Asn Lys Leu Cys Gly 770 775 780 Asn Ser Arg GlnMet Ala Cys Thr Pro Ile Ser Cys Pro Gly Glu Leu 785 790 795 800 Cys ProGln Asp Asn Gly Thr Ala Cys Gly Ser Arg Cys Arg Gly Val 805 810 815 LeuPro Arg Ala Gly Gly Ala Phe Leu Met Ala Gly Gln Val Ala Glu 820 825 830Gln Leu Arg Gly Phe Asn Ala Gln Leu Gln Arg Thr Arg Gln Met Ile 835 840845 Arg Ala Ala Glu Glu Ser Ala Ser Gln Ile Gln Ser Ser Ala Gln Arg 850855 860 Leu Glu Thr Gln Val Ser Ala Ser Arg Ser Gln Met Glu Glu Asp Val865 870 875 880 Arg Arg Thr Arg Leu Leu Ile Gln Gln Val Arg Asp Phe LeuThr Asp 885 890 895 Pro Asp Thr Asp Ala Ala Thr Ile Gln Glu Val Ser GluAla Val Leu 900 905 910 Ala Leu Trp Leu Pro Thr Asp Ser Ala Thr Val LeuGln Lys Met Asn 915 920 925 Glu Ile Gln Ala Ile Ala Ala Arg Leu Pro AsnVal Asp Leu Val Leu 930 935 940 Ser Gln Thr Lys Gln Asp Ile Ala Arg AlaArg Arg Leu Gln Ala Glu 945 950 955 960 Ala Glu Glu Ala Arg Ser Arg AlaHis Ala Val Glu Gly Gln Val Glu 965 970 975 Asp Val Val Gly Asn Leu ArgGln Gly Thr Val Ala Leu Gln Glu Ala 980 985 990 Gln Asp Thr Met Gln GlyThr Ser Arg Ser Leu Arg Leu Ile Gln Asp 995 1000 1005 Arg Val Ala GluVal Gln Gln Val Leu Arg Pro Ala Glu Lys Leu Val 1010 1015 1020 Thr SerMet Thr Lys Gln Leu Gly Asp Phe Trp Thr Arg Met Glu Glu 1025 1030 10351040 Leu Arg His Gln Ala Arg Gln Gln Gly Ala Glu Ala Val Gln Ala Gln1045 1050 1055 Gln Leu Ala Glu Gly Ala Ser Glu Gln Ala Leu Ser Ala GlnGlu Gly 1060 1065 1070 Phe Glu Arg Ile Lys Gln Lys Tyr Ala Glu Leu LysAsp Arg Leu Gly 1075 1080 1085 Gln Ser Ser Met Leu Gly Glu Gln Gly AlaArg Ile Gln Ser Val Lys 1090 1095 1100 Thr Glu Ala Glu Glu Leu Phe GlyGlu Thr Met Glu Met Met Asp Arg 1105 1110 1115 1120 Met Lys Asp Met GluLeu Glu Leu Leu Arg Gly Ser Gln Ala Ile Met 1125 1130 1135 Leu Arg SerAla Asp Leu Thr Gly Leu Glu Lys Arg Val Glu Gln Ile 1140 1145 1150 ArgAsp His Ile Asn Gly Arg Val Leu Tyr Tyr Ala Thr Cys Lys 1155 1160 116521 3585 DNA Homo sapiens CDS (60)..(3581) sig_peptide (60)..(116) 21gtttaaactt aagcttctgc ctgccgcctg cctgcctgcc actgagggtt cccagcacc 59 atgagg gcc tgg atc ttc ttt ctc ctt tgc ctg gcc ggg agg gct ctg 107 Met ArgAla Trp Ile Phe Phe Leu Leu Cys Leu Ala Gly Arg Ala Leu 1 5 10 15 gcagcc cca caa caa gcc tgc tcc cgt ggg gcc tgc tat cca cct gtt 155 Ala AlaPro Gln Gln Ala Cys Ser Arg Gly Ala Cys Tyr Pro Pro Val 20 25 30 ggg gacctg ctt gtt ggg agg acc cgg ttt ctc cga gct tca tct acc 203 Gly Asp LeuLeu Val Gly Arg Thr Arg Phe Leu Arg Ala Ser Ser Thr 35 40 45 tgt gga ctgacc aag cct gag acc tac tgc acc cag tat ggc gag tgg 251 Cys Gly Leu ThrLys Pro Glu Thr Tyr Cys Thr Gln Tyr Gly Glu Trp 50 55 60 cag atg aaa tgctgc aag tgt gac tcc agg cag cct cac aac tac tac 299 Gln Met Lys Cys CysLys Cys Asp Ser Arg Gln Pro His Asn Tyr Tyr 65 70 75 80 agt cac cga gtagag aat gtg gct tca tcc tcc ggc ccc atg cgc tgg 347 Ser His Arg Val GluAsn Val Ala Ser Ser Ser Gly Pro Met Arg Trp 85 90 95 tgg cag tcc cag aatgat gtg aac cct gtc tct ctg cag ctg gac ctg 395 Trp Gln Ser Gln Asn AspVal Asn Pro Val Ser Leu Gln Leu Asp Leu 100 105 110 gac agg aga ttc cagctt caa gaa gtc atg atg gag ttc cag ggg ccc 443 Asp Arg Arg Phe Gln LeuGln Glu Val Met Met Glu Phe Gln Gly Pro 115 120 125 atg cct gcc ggc atgctg att gag cgc tcc tca gac ttc ggt aag acc 491 Met Pro Ala Gly Met LeuIle Glu Arg Ser Ser Asp Phe Gly Lys Thr 130 135 140 tgg cga gtg tac cagtac ctg gct gcc gac tgc acc tcc acc ttc cct 539 Trp Arg Val Tyr Gln TyrLeu Ala Ala Asp Cys Thr Ser Thr Phe Pro 145 150 155 160 cgg gtc cgc cagggt cgg cct cag agc tgg cag gat gtt cgg tgc cag 587 Arg Val Arg Gln GlyArg Pro Gln Ser Trp Gln Asp Val Arg Cys Gln 165 170 175 tcc ctg cct cagagg cct aat gca cgc cta aat ggg ggg aag gtc caa 635 Ser Leu Pro Gln ArgPro Asn Ala Arg Leu Asn Gly Gly Lys Val Gln 180 185 190 ctt aac ctt atggat tta gtg tct ggg att cca gca act caa agt caa 683 Leu Asn Leu Met AspLeu Val Ser Gly Ile Pro Ala Thr Gln Ser Gln 195 200 205 aaa att caa gaggtg ggg gag atc aca aac ttg aga gtc aat ttc acc 731 Lys Ile Gln Glu ValGly Glu Ile Thr Asn Leu Arg Val Asn Phe Thr 210 215 220 agg ctg gcc cctgtg ccc caa agg ggc tac cac cct ccc agc gcc tac 779 Arg Leu Ala Pro ValPro Gln Arg Gly Tyr His Pro Pro Ser Ala Tyr 225 230 235 240 tat gct gtgtcc cag ctc cgt ctg cag ggg agc tgc ttc tgt cac ggc 827 Tyr Ala Val SerGln Leu Arg Leu Gln Gly Ser Cys Phe Cys His Gly 245 250 255 cat gct gatcgc tgc gca ccc aag cct ggg gcc tct gca ggc ccc tcc 875 His Ala Asp ArgCys Ala Pro Lys Pro Gly Ala Ser Ala Gly Pro Ser 260 265 270 acc gct gtgcag gtc cac gat gtc tgc gtc tgc cag cac aac act gcc 923 Thr Ala Val GlnVal His Asp Val Cys Val Cys Gln His Asn Thr Ala 275 280 285 ggc cca aattgt gag cgc tgt gca ccc ttc tac aac aac cgg ccc tgg 971 Gly Pro Asn CysGlu Arg Cys Ala Pro Phe Tyr Asn Asn Arg Pro Trp 290 295 300 aga ccg gcggag ggc cag gac gcc cat gaa tgc caa agg tgc gac tgc 1019 Arg Pro Ala GluGly Gln Asp Ala His Glu Cys Gln Arg Cys Asp Cys 305 310 315 320 aat gggcac tca gag aca tgt cac ttt gac ccc gct gtg ttt gcc gcc 1067 Asn Gly HisSer Glu Thr Cys His Phe Asp Pro Ala Val Phe Ala Ala 325 330 335 agc cagggg gca tat gga ggt gtg tgt gac aat tgc cgg gac cac acc 1115 Ser Gln GlyAla Tyr Gly Gly Val Cys Asp Asn Cys Arg Asp His Thr 340 345 350 gaa ggcaag aac tgt gag cgg tgt cag ctg cac tat ttc cgg aac cgg 1163 Glu Gly LysAsn Cys Glu Arg Cys Gln Leu His Tyr Phe Arg Asn Arg 355 360 365 cgc ccggga gct tcc att cag gag acc tgc atc tcc tgc gag tgt gat 1211 Arg Pro GlyAla Ser Ile Gln Glu Thr Cys Ile Ser Cys Glu Cys Asp 370 375 380 ccg gatggg gca gtg cca ggg gct ccc tgt gac cca gtg acc ggg cag 1259 Pro Asp GlyAla Val Pro Gly Ala Pro Cys Asp Pro Val Thr Gly Gln 385 390 395 400 tgtgtg tgc aag gag cat gtg cag gga gag cgc tgt gac cta tgc aag 1307 Cys ValCys Lys Glu His Val Gln Gly Glu Arg Cys Asp Leu Cys Lys 405 410 415 ccgggc ttc act gga ctc acc tac gcc aac ccg cag ggc tgc cac cgc 1355 Pro GlyPhe Thr Gly Leu Thr Tyr Ala Asn Pro Gln Gly Cys His Arg 420 425 430 tgtgac tgc aac atc ctg ggg tcc cgg agg gac atg ccg tgt gac gag 1403 Cys AspCys Asn Ile Leu Gly Ser Arg Arg Asp Met Pro Cys Asp Glu 435 440 445 gagagt ggg cgc tgc ctt tgt ctg ccc aac gtg gtg ggt ccc aaa tgt 1451 Glu SerGly Arg Cys Leu Cys Leu Pro Asn Val Val Gly Pro Lys Cys 450 455 460 gaccag tgt gct ccc tac cac tgg aag ctg gcc agt ggc cag ggc tgt 1499 Asp GlnCys Ala Pro Tyr His Trp Lys Leu Ala Ser Gly Gln Gly Cys 465 470 475 480gaa ccg tgt gcc tgc gac ccg cac aac tcc ctc agc cca cag tgc aac 1547 GluPro Cys Ala Cys Asp Pro His Asn Ser Leu Ser Pro Gln Cys Asn 485 490 495cag ttc aca ggg cag tgc ccc tgt cgg gaa ggc ttt ggt ggc ctg atg 1595 GlnPhe Thr Gly Gln Cys Pro Cys Arg Glu Gly Phe Gly Gly Leu Met 500 505 510tgc agc gct gca gcc atc cgc cag tgt cca gac cgg acc tat gga gac 1643 CysSer Ala Ala Ala Ile Arg Gln Cys Pro Asp Arg Thr Tyr Gly Asp 515 520 525gtg gcc aca gga tgc cga gcc tgt gac tgt gat ttc cgg gga aca gag 1691 ValAla Thr Gly Cys Arg Ala Cys Asp Cys Asp Phe Arg Gly Thr Glu 530 535 540ggc ccg ggc tgc gac aag gca tca ggc cgc tgc ctc tgc cgc cct ggc 1739 GlyPro Gly Cys Asp Lys Ala Ser Gly Arg Cys Leu Cys Arg Pro Gly 545 550 555560 ttg acc ggg ccc cgc tgt gac cag tgc cag cga ggc tac tgc aat cgc 1787Leu Thr Gly Pro Arg Cys Asp Gln Cys Gln Arg Gly Tyr Cys Asn Arg 565 570575 tac ccg gtg tgc gtg gcc tgc cac cct tgc ttc cag acc tat gat gcg 1835Tyr Pro Val Cys Val Ala Cys His Pro Cys Phe Gln Thr Tyr Asp Ala 580 585590 gac ctc cgg gag cag gcc ctg cgc ttt ggt aga ctc cgg aat gcc acc 1883Asp Leu Arg Glu Gln Ala Leu Arg Phe Gly Arg Leu Arg Asn Ala Thr 595 600605 gcc agc ctg tgg tca ggg cct ggg ctg gag gac cgt ggc ctg gcc tcc 1931Ala Ser Leu Trp Ser Gly Pro Gly Leu Glu Asp Arg Gly Leu Ala Ser 610 615620 cgg atc cta gat gca aag agt aag att gag cag atc cga gca gtt ctc 1979Arg Ile Leu Asp Ala Lys Ser Lys Ile Glu Gln Ile Arg Ala Val Leu 625 630635 640 agc agc ccc gca gtc aca gag cag gag gtg gct cag gtg gcc agt gcc2027 Ser Ser Pro Ala Val Thr Glu Gln Glu Val Ala Gln Val Ala Ser Ala 645650 655 atc ctc tcc ctc agg cga act ctc cag ggc ctg cag ctg gat ctg ccc2075 Ile Leu Ser Leu Arg Arg Thr Leu Gln Gly Leu Gln Leu Asp Leu Pro 660665 670 ctg gag gag gag acg ttg tcc ctt ccg aga gac ctg gag agt ctt gac2123 Leu Glu Glu Glu Thr Leu Ser Leu Pro Arg Asp Leu Glu Ser Leu Asp 675680 685 aga agc ttc aat ggt ctc ctt act atg tat cag agg aag agg gag cag2171 Arg Ser Phe Asn Gly Leu Leu Thr Met Tyr Gln Arg Lys Arg Glu Gln 690695 700 ttt gaa aaa ata agc agt gct gat cct tca gga gcc ttc cgg atg ctg2219 Phe Glu Lys Ile Ser Ser Ala Asp Pro Ser Gly Ala Phe Arg Met Leu 705710 715 720 agc aca gcc tac gag cag tca gcc cag gct gct cag cag gtc tccgac 2267 Ser Thr Ala Tyr Glu Gln Ser Ala Gln Ala Ala Gln Gln Val Ser Asp725 730 735 agc tcg cgc ctt ttg gac cag ctc agg gac agc cgg aga gag gcagag 2315 Ser Ser Arg Leu Leu Asp Gln Leu Arg Asp Ser Arg Arg Glu Ala Glu740 745 750 agg ctg gtg cgg cag gcg gga gga gga gga ggc acc ggc agc cccaag 2363 Arg Leu Val Arg Gln Ala Gly Gly Gly Gly Gly Thr Gly Ser Pro Lys755 760 765 ctt gtg gcc ctg agg ctg gag atg tct tcg ttg cct gac ctg acaccc 2411 Leu Val Ala Leu Arg Leu Glu Met Ser Ser Leu Pro Asp Leu Thr Pro770 775 780 acc ttc aac aag ctc tgt ggc aac tcc agg cag atg gct tgc acccca 2459 Thr Phe Asn Lys Leu Cys Gly Asn Ser Arg Gln Met Ala Cys Thr Pro785 790 795 800 ata tca tgc cct ggt gag cta tgt ccc caa gac aat ggc acagcc tgt 2507 Ile Ser Cys Pro Gly Glu Leu Cys Pro Gln Asp Asn Gly Thr AlaCys 805 810 815 ggc tcc cgc tgc agg ggt gtc ctt ccc agg gcc ggt ggg gccttc ttg 2555 Gly Ser Arg Cys Arg Gly Val Leu Pro Arg Ala Gly Gly Ala PheLeu 820 825 830 atg gcg ggg cag gtg gct gag cag ctg cgg ggc ttc aat gcccag ctc 2603 Met Ala Gly Gln Val Ala Glu Gln Leu Arg Gly Phe Asn Ala GlnLeu 835 840 845 cag cgg acc agg cag atg att agg gca gcc gag gaa tct gcctca cag 2651 Gln Arg Thr Arg Gln Met Ile Arg Ala Ala Glu Glu Ser Ala SerGln 850 855 860 att caa tcc agt gcc cag cgc ttg gag acc cag gtg agc gccagc cgc 2699 Ile Gln Ser Ser Ala Gln Arg Leu Glu Thr Gln Val Ser Ala SerArg 865 870 875 880 tcc cag atg gag gaa gat gtc aga cgc aca cgg ctc ctaatc cag cag 2747 Ser Gln Met Glu Glu Asp Val Arg Arg Thr Arg Leu Leu IleGln Gln 885 890 895 gtc cgg gac ttc cta aca gac ccc gac act gat gca gccact atc cag 2795 Val Arg Asp Phe Leu Thr Asp Pro Asp Thr Asp Ala Ala ThrIle Gln 900 905 910 gag gtc agc gag gcc gtg ctg gcc ctg tgg ctg ccc acagac tca gct 2843 Glu Val Ser Glu Ala Val Leu Ala Leu Trp Leu Pro Thr AspSer Ala 915 920 925 act gtt ctg cag aag atg aat gag atc cag gcc att gcagcc agg ctc 2891 Thr Val Leu Gln Lys Met Asn Glu Ile Gln Ala Ile Ala AlaArg Leu 930 935 940 ccc aac gtg gac ttg gtg ctg tcc cag acc aag cag gacatt gcg cgt 2939 Pro Asn Val Asp Leu Val Leu Ser Gln Thr Lys Gln Asp IleAla Arg 945 950 955 960 gcc cgc cgg ttg cag gct gag gct gag gaa gcc aggagc cga gcc cat 2987 Ala Arg Arg Leu Gln Ala Glu Ala Glu Glu Ala Arg SerArg Ala His 965 970 975 gca gtg gag ggc cag gtg gaa gat gtg gtt ggg aacctg cgg cag ggg 3035 Ala Val Glu Gly Gln Val Glu Asp Val Val Gly Asn LeuArg Gln Gly 980 985 990 aca gtg gca ctg cag gaa gct cag gac acc atg caaggc acc agc cgc 3083 Thr Val Ala Leu Gln Glu Ala Gln Asp Thr Met Gln GlyThr Ser Arg 995 1000 1005 tcc ctt cgg ctt atc cag gac agg gtt gct gaggtt cag cag gta ctg 3131 Ser Leu Arg Leu Ile Gln Asp Arg Val Ala Glu ValGln Gln Val Leu 1010 1015 1020 cgg cca gca gaa aag ctg gtg aca agc atgacc aag cag ctg ggt gac 3179 Arg Pro Ala Glu Lys Leu Val Thr Ser Met ThrLys Gln Leu Gly Asp 1025 1030 1035 1040 ttc tgg aca cgg atg gag gag ctccgc cac caa gcc cgg cag cag ggg 3227 Phe Trp Thr Arg Met Glu Glu Leu ArgHis Gln Ala Arg Gln Gln Gly 1045 1050 1055 gca gag gca gtc cag gcc cagcag ctt gcg gaa ggt gcc agc gag cag 3275 Ala Glu Ala Val Gln Ala Gln GlnLeu Ala Glu Gly Ala Ser Glu Gln 1060 1065 1070 gca ttg agt gcc caa gaggga ttt gag aga ata aaa caa aag tat gct 3323 Ala Leu Ser Ala Gln Glu GlyPhe Glu Arg Ile Lys Gln Lys Tyr Ala 1075 1080 1085 gag ttg aag gac cggttg ggt cag agt tcc atg ctg ggt gag cag ggt 3371 Glu Leu Lys Asp Arg LeuGly Gln Ser Ser Met Leu Gly Glu Gln Gly 1090 1095 1100 gcc cgg atc cagagt gtg aag aca gag gca gag gag ctg ttt ggg gag 3419 Ala Arg Ile Gln SerVal Lys Thr Glu Ala Glu Glu Leu Phe Gly Glu 1105 1110 1115 1120 acc atggag atg atg gac agg atg aaa gac atg gag ttg gag ctg ctg 3467 Thr Met GluMet Met Asp Arg Met Lys Asp Met Glu Leu Glu Leu Leu 1125 1130 1135 cggggc agc cag gcc atc atg ctg cgc tca gcg gac ctg aca gga ctg 3515 Arg GlySer Gln Ala Ile Met Leu Arg Ser Ala Asp Leu Thr Gly Leu 1140 1145 1150gag aag cgt gtg gag cag atc cgt gac cac atc aat ggg cgc gtg ctc 3563 GluLys Arg Val Glu Gln Ile Arg Asp His Ile Asn Gly Arg Val Leu 1155 11601165 tac tat gcc acc tgc aag tgat 3585 Tyr Tyr Ala Thr Cys Lys 1170 221174 PRT Homo sapiens 22 Met Arg Ala Trp Ile Phe Phe Leu Leu Cys Leu AlaGly Arg Ala Leu 1 5 10 15 Ala Ala Pro Gln Gln Ala Cys Ser Arg Gly AlaCys Tyr Pro Pro Val 20 25 30 Gly Asp Leu Leu Val Gly Arg Thr Arg Phe LeuArg Ala Ser Ser Thr 35 40 45 Cys Gly Leu Thr Lys Pro Glu Thr Tyr Cys ThrGln Tyr Gly Glu Trp 50 55 60 Gln Met Lys Cys Cys Lys Cys Asp Ser Arg GlnPro His Asn Tyr Tyr 65 70 75 80 Ser His Arg Val Glu Asn Val Ala Ser SerSer Gly Pro Met Arg Trp 85 90 95 Trp Gln Ser Gln Asn Asp Val Asn Pro ValSer Leu Gln Leu Asp Leu 100 105 110 Asp Arg Arg Phe Gln Leu Gln Glu ValMet Met Glu Phe Gln Gly Pro 115 120 125 Met Pro Ala Gly Met Leu Ile GluArg Ser Ser Asp Phe Gly Lys Thr 130 135 140 Trp Arg Val Tyr Gln Tyr LeuAla Ala Asp Cys Thr Ser Thr Phe Pro 145 150 155 160 Arg Val Arg Gln GlyArg Pro Gln Ser Trp Gln Asp Val Arg Cys Gln 165 170 175 Ser Leu Pro GlnArg Pro Asn Ala Arg Leu Asn Gly Gly Lys Val Gln 180 185 190 Leu Asn LeuMet Asp Leu Val Ser Gly Ile Pro Ala Thr Gln Ser Gln 195 200 205 Lys IleGln Glu Val Gly Glu Ile Thr Asn Leu Arg Val Asn Phe Thr 210 215 220 ArgLeu Ala Pro Val Pro Gln Arg Gly Tyr His Pro Pro Ser Ala Tyr 225 230 235240 Tyr Ala Val Ser Gln Leu Arg Leu Gln Gly Ser Cys Phe Cys His Gly 245250 255 His Ala Asp Arg Cys Ala Pro Lys Pro Gly Ala Ser Ala Gly Pro Ser260 265 270 Thr Ala Val Gln Val His Asp Val Cys Val Cys Gln His Asn ThrAla 275 280 285 Gly Pro Asn Cys Glu Arg Cys Ala Pro Phe Tyr Asn Asn ArgPro Trp 290 295 300 Arg Pro Ala Glu Gly Gln Asp Ala His Glu Cys Gln ArgCys Asp Cys 305 310 315 320 Asn Gly His Ser Glu Thr Cys His Phe Asp ProAla Val Phe Ala Ala 325 330 335 Ser Gln Gly Ala Tyr Gly Gly Val Cys AspAsn Cys Arg Asp His Thr 340 345 350 Glu Gly Lys Asn Cys Glu Arg Cys GlnLeu His Tyr Phe Arg Asn Arg 355 360 365 Arg Pro Gly Ala Ser Ile Gln GluThr Cys Ile Ser Cys Glu Cys Asp 370 375 380 Pro Asp Gly Ala Val Pro GlyAla Pro Cys Asp Pro Val Thr Gly Gln 385 390 395 400 Cys Val Cys Lys GluHis Val Gln Gly Glu Arg Cys Asp Leu Cys Lys 405 410 415 Pro Gly Phe ThrGly Leu Thr Tyr Ala Asn Pro Gln Gly Cys His Arg 420 425 430 Cys Asp CysAsn Ile Leu Gly Ser Arg Arg Asp Met Pro Cys Asp Glu 435 440 445 Glu SerGly Arg Cys Leu Cys Leu Pro Asn Val Val Gly Pro Lys Cys 450 455 460 AspGln Cys Ala Pro Tyr His Trp Lys Leu Ala Ser Gly Gln Gly Cys 465 470 475480 Glu Pro Cys Ala Cys Asp Pro His Asn Ser Leu Ser Pro Gln Cys Asn 485490 495 Gln Phe Thr Gly Gln Cys Pro Cys Arg Glu Gly Phe Gly Gly Leu Met500 505 510 Cys Ser Ala Ala Ala Ile Arg Gln Cys Pro Asp Arg Thr Tyr GlyAsp 515 520 525 Val Ala Thr Gly Cys Arg Ala Cys Asp Cys Asp Phe Arg GlyThr Glu 530 535 540 Gly Pro Gly Cys Asp Lys Ala Ser Gly Arg Cys Leu CysArg Pro Gly 545 550 555 560 Leu Thr Gly Pro Arg Cys Asp Gln Cys Gln ArgGly Tyr Cys Asn Arg 565 570 575 Tyr Pro Val Cys Val Ala Cys His Pro CysPhe Gln Thr Tyr Asp Ala 580 585 590 Asp Leu Arg Glu Gln Ala Leu Arg PheGly Arg Leu Arg Asn Ala Thr 595 600 605 Ala Ser Leu Trp Ser Gly Pro GlyLeu Glu Asp Arg Gly Leu Ala Ser 610 615 620 Arg Ile Leu Asp Ala Lys SerLys Ile Glu Gln Ile Arg Ala Val Leu 625 630 635 640 Ser Ser Pro Ala ValThr Glu Gln Glu Val Ala Gln Val Ala Ser Ala 645 650 655 Ile Leu Ser LeuArg Arg Thr Leu Gln Gly Leu Gln Leu Asp Leu Pro 660 665 670 Leu Glu GluGlu Thr Leu Ser Leu Pro Arg Asp Leu Glu Ser Leu Asp 675 680 685 Arg SerPhe Asn Gly Leu Leu Thr Met Tyr Gln Arg Lys Arg Glu Gln 690 695 700 PheGlu Lys Ile Ser Ser Ala Asp Pro Ser Gly Ala Phe Arg Met Leu 705 710 715720 Ser Thr Ala Tyr Glu Gln Ser Ala Gln Ala Ala Gln Gln Val Ser Asp 725730 735 Ser Ser Arg Leu Leu Asp Gln Leu Arg Asp Ser Arg Arg Glu Ala Glu740 745 750 Arg Leu Val Arg Gln Ala Gly Gly Gly Gly Gly Thr Gly Ser ProLys 755 760 765 Leu Val Ala Leu Arg Leu Glu Met Ser Ser Leu Pro Asp LeuThr Pro 770 775 780 Thr Phe Asn Lys Leu Cys Gly Asn Ser Arg Gln Met AlaCys Thr Pro 785 790 795 800 Ile Ser Cys Pro Gly Glu Leu Cys Pro Gln AspAsn Gly Thr Ala Cys 805 810 815 Gly Ser Arg Cys Arg Gly Val Leu Pro ArgAla Gly Gly Ala Phe Leu 820 825 830 Met Ala Gly Gln Val Ala Glu Gln LeuArg Gly Phe Asn Ala Gln Leu 835 840 845 Gln Arg Thr Arg Gln Met Ile ArgAla Ala Glu Glu Ser Ala Ser Gln 850 855 860 Ile Gln Ser Ser Ala Gln ArgLeu Glu Thr Gln Val Ser Ala Ser Arg 865 870 875 880 Ser Gln Met Glu GluAsp Val Arg Arg Thr Arg Leu Leu Ile Gln Gln 885 890 895 Val Arg Asp PheLeu Thr Asp Pro Asp Thr Asp Ala Ala Thr Ile Gln 900 905 910 Glu Val SerGlu Ala Val Leu Ala Leu Trp Leu Pro Thr Asp Ser Ala 915 920 925 Thr ValLeu Gln Lys Met Asn Glu Ile Gln Ala Ile Ala Ala Arg Leu 930 935 940 ProAsn Val Asp Leu Val Leu Ser Gln Thr Lys Gln Asp Ile Ala Arg 945 950 955960 Ala Arg Arg Leu Gln Ala Glu Ala Glu Glu Ala Arg Ser Arg Ala His 965970 975 Ala Val Glu Gly Gln Val Glu Asp Val Val Gly Asn Leu Arg Gln Gly980 985 990 Thr Val Ala Leu Gln Glu Ala Gln Asp Thr Met Gln Gly Thr SerArg 995 1000 1005 Ser Leu Arg Leu Ile Gln Asp Arg Val Ala Glu Val GlnGln Val Leu 1010 1015 1020 Arg Pro Ala Glu Lys Leu Val Thr Ser Met ThrLys Gln Leu Gly Asp 1025 1030 1035 1040 Phe Trp Thr Arg Met Glu Glu LeuArg His Gln Ala Arg Gln Gln Gly 1045 1050 1055 Ala Glu Ala Val Gln AlaGln Gln Leu Ala Glu Gly Ala Ser Glu Gln 1060 1065 1070 Ala Leu Ser AlaGln Glu Gly Phe Glu Arg Ile Lys Gln Lys Tyr Ala 1075 1080 1085 Glu LeuLys Asp Arg Leu Gly Gln Ser Ser Met Leu Gly Glu Gln Gly 1090 1095 1100Ala Arg Ile Gln Ser Val Lys Thr Glu Ala Glu Glu Leu Phe Gly Glu 11051110 1115 1120 Thr Met Glu Met Met Asp Arg Met Lys Asp Met Glu Leu GluLeu Leu 1125 1130 1135 Arg Gly Ser Gln Ala Ile Met Leu Arg Ser Ala AspLeu Thr Gly Leu 1140 1145 1150 Glu Lys Arg Val Glu Gln Ile Arg Asp HisIle Asn Gly Arg Val Leu 1155 1160 1165 Tyr Tyr Ala Thr Cys Lys 1170 233469 DNA Homo sapiens CDS (1)..(3465) 23 caa caa gcc tgc tcc cgt ggg gcctgc tat cca cct gtt ggg gac ctg 48 Gln Gln Ala Cys Ser Arg Gly Ala CysTyr Pro Pro Val Gly Asp Leu 1 5 10 15 ctt gtt ggg agg acc cgg ttt ctccga gct tca tct acc tgt gga ctg 96 Leu Val Gly Arg Thr Arg Phe Leu ArgAla Ser Ser Thr Cys Gly Leu 20 25 30 acc aag cct gag acc tac tgc acc cagtat ggc gag tgg cag atg aaa 144 Thr Lys Pro Glu Thr Tyr Cys Thr Gln TyrGly Glu Trp Gln Met Lys 35 40 45 tgc tgc aag tgt gac tcc agg cag cct cacaac tac tac agt cac cga 192 Cys Cys Lys Cys Asp Ser Arg Gln Pro His AsnTyr Tyr Ser His Arg 50 55 60 gta gag aat gtg gct tca tcc tcc ggc ccc atgcgc tgg tgg cag tcc 240 Val Glu Asn Val Ala Ser Ser Ser Gly Pro Met ArgTrp Trp Gln Ser 65 70 75 80 cag aat gat gtg aac cct gtc tct ctg cag ctggac ctg gac agg aga 288 Gln Asn Asp Val Asn Pro Val Ser Leu Gln Leu AspLeu Asp Arg Arg 85 90 95 ttc cag ctt caa gaa gtc atg atg gag ttc cag gggccc atg cct gcc 336 Phe Gln Leu Gln Glu Val Met Met Glu Phe Gln Gly ProMet Pro Ala 100 105 110 ggc atg ctg att gag cgc tcc tca gac ttc ggt aagacc tgg cga gtg 384 Gly Met Leu Ile Glu Arg Ser Ser Asp Phe Gly Lys ThrTrp Arg Val 115 120 125 tac cag tac ctg gct gcc gac tgc acc tcc acc ttccct cgg gtc cgc 432 Tyr Gln Tyr Leu Ala Ala Asp Cys Thr Ser Thr Phe ProArg Val Arg 130 135 140 cag ggt cgg cct cag agc tgg cag gat gtt cgg tgccag tcc ctg cct 480 Gln Gly Arg Pro Gln Ser Trp Gln Asp Val Arg Cys GlnSer Leu Pro 145 150 155 160 cag agg cct aat gca cgc cta aat ggg ggg aaggtc caa ctt aac ctt 528 Gln Arg Pro Asn Ala Arg Leu Asn Gly Gly Lys ValGln Leu Asn Leu 165 170 175 atg gat tta gtg tct ggg att cca gca act caaagt caa aaa att caa 576 Met Asp Leu Val Ser Gly Ile Pro Ala Thr Gln SerGln Lys Ile Gln 180 185 190 gag gtg ggg gag atc aca aac ttg aga gtc aatttc acc agg ctg gcc 624 Glu Val Gly Glu Ile Thr Asn Leu Arg Val Asn PheThr Arg Leu Ala 195 200 205 cct gtg ccc caa agg ggc tac cac cct ccc agcgcc tac tat gct gtg 672 Pro Val Pro Gln Arg Gly Tyr His Pro Pro Ser AlaTyr Tyr Ala Val 210 215 220 tcc cag ctc cgt ctg cag ggg agc tgc ttc tgtcac ggc cat gct gat 720 Ser Gln Leu Arg Leu Gln Gly Ser Cys Phe Cys HisGly His Ala Asp 225 230 235 240 cgc tgc gca ccc aag cct ggg gcc tct gcaggc ccc tcc acc gct gtg 768 Arg Cys Ala Pro Lys Pro Gly Ala Ser Ala GlyPro Ser Thr Ala Val 245 250 255 cag gtc cac gat gtc tgc gtc tgc cag cacaac act gcc ggc cca aat 816 Gln Val His Asp Val Cys Val Cys Gln His AsnThr Ala Gly Pro Asn 260 265 270 tgt gag cgc tgt gca ccc ttc tac aac aaccgg ccc tgg aga ccg gcg 864 Cys Glu Arg Cys Ala Pro Phe Tyr Asn Asn ArgPro Trp Arg Pro Ala 275 280 285 gag ggc cag gac gcc cat gaa tgc caa aggtgc gac tgc aat ggg cac 912 Glu Gly Gln Asp Ala His Glu Cys Gln Arg CysAsp Cys Asn Gly His 290 295 300 tca gag aca tgt cac ttt gac ccc gct gtgttt gcc gcc agc cag ggg 960 Ser Glu Thr Cys His Phe Asp Pro Ala Val PheAla Ala Ser Gln Gly 305 310 315 320 gca tat gga ggt gtg tgt gac aat tgccgg gac cac acc gaa ggc aag 1008 Ala Tyr Gly Gly Val Cys Asp Asn Cys ArgAsp His Thr Glu Gly Lys 325 330 335 aac tgt gag cgg tgt cag ctg cac tatttc cgg aac cgg cgc ccg gga 1056 Asn Cys Glu Arg Cys Gln Leu His Tyr PheArg Asn Arg Arg Pro Gly 340 345 350 gct tcc att cag gag acc tgc atc tcctgc gag tgt gat ccg gat ggg 1104 Ala Ser Ile Gln Glu Thr Cys Ile Ser CysGlu Cys Asp Pro Asp Gly 355 360 365 gca gtg cca ggg gct ccc tgt gac ccagtg acc ggg cag tgt gtg tgc 1152 Ala Val Pro Gly Ala Pro Cys Asp Pro ValThr Gly Gln Cys Val Cys 370 375 380 aag gag cat gtg cag gga gag cgc tgtgac cta tgc aag ccg ggc ttc 1200 Lys Glu His Val Gln Gly Glu Arg Cys AspLeu Cys Lys Pro Gly Phe 385 390 395 400 act gga ctc acc tac gcc aac ccgcag ggc tgc cac cgc tgt gac tgc 1248 Thr Gly Leu Thr Tyr Ala Asn Pro GlnGly Cys His Arg Cys Asp Cys 405 410 415 aac atc ctg ggg tcc cgg agg gacatg ccg tgt gac gag gag agt ggg 1296 Asn Ile Leu Gly Ser Arg Arg Asp MetPro Cys Asp Glu Glu Ser Gly 420 425 430 cgc tgc ctt tgt ctg ccc aac gtggtg ggt ccc aaa tgt gac cag tgt 1344 Arg Cys Leu Cys Leu Pro Asn Val ValGly Pro Lys Cys Asp Gln Cys 435 440 445 gct ccc tac cac tgg aag ctg gccagt ggc cag ggc tgt gaa ccg tgt 1392 Ala Pro Tyr His Trp Lys Leu Ala SerGly Gln Gly Cys Glu Pro Cys 450 455 460 gcc tgc gac ccg cac aac tcc ctcagc cca cag tgc aac cag ttc aca 1440 Ala Cys Asp Pro His Asn Ser Leu SerPro Gln Cys Asn Gln Phe Thr 465 470 475 480 ggg cag tgc ccc tgt cgg gaaggc ttt ggt ggc ctg atg tgc agc gct 1488 Gly Gln Cys Pro Cys Arg Glu GlyPhe Gly Gly Leu Met Cys Ser Ala 485 490 495 gca gcc atc cgc cag tgt ccagac cgg acc tat gga gac gtg gcc aca 1536 Ala Ala Ile Arg Gln Cys Pro AspArg Thr Tyr Gly Asp Val Ala Thr 500 505 510 gga tgc cga gcc tgt gac tgtgat ttc cgg gga aca gag ggc ccg ggc 1584 Gly Cys Arg Ala Cys Asp Cys AspPhe Arg Gly Thr Glu Gly Pro Gly 515 520 525 tgc gac aag gca tca ggc cgctgc ctc tgc cgc cct ggc ttg acc ggg 1632 Cys Asp Lys Ala Ser Gly Arg CysLeu Cys Arg Pro Gly Leu Thr Gly 530 535 540 ccc cgc tgt gac cag tgc cagcga ggc tac tgc aat cgc tac ccg gtg 1680 Pro Arg Cys Asp Gln Cys Gln ArgGly Tyr Cys Asn Arg Tyr Pro Val 545 550 555 560 tgc gtg gcc tgc cac ccttgc ttc cag acc tat gat gcg gac ctc cgg 1728 Cys Val Ala Cys His Pro CysPhe Gln Thr Tyr Asp Ala Asp Leu Arg 565 570 575 gag cag gcc ctg cgc tttggt aga ctc cgg aat gcc acc gcc agc ctg 1776 Glu Gln Ala Leu Arg Phe GlyArg Leu Arg Asn Ala Thr Ala Ser Leu 580 585 590 tgg tca ggg cct ggg ctggag gac cgt ggc ctg gcc tcc cgg atc cta 1824 Trp Ser Gly Pro Gly Leu GluAsp Arg Gly Leu Ala Ser Arg Ile Leu 595 600 605 gat gca aag agt aag attgag cag atc cga gca gtt ctc agc agc ccc 1872 Asp Ala Lys Ser Lys Ile GluGln Ile Arg Ala Val Leu Ser Ser Pro 610 615 620 gca gtc aca gag cag gaggtg gct cag gtg gcc agt gcc atc ctc tcc 1920 Ala Val Thr Glu Gln Glu ValAla Gln Val Ala Ser Ala Ile Leu Ser 625 630 635 640 ctc agg cga act ctccag ggc ctg cag ctg gat ctg ccc ctg gag gag 1968 Leu Arg Arg Thr Leu GlnGly Leu Gln Leu Asp Leu Pro Leu Glu Glu 645 650 655 gag acg ttg tcc cttccg aga gac ctg gag agt ctt gac aga agc ttc 2016 Glu Thr Leu Ser Leu ProArg Asp Leu Glu Ser Leu Asp Arg Ser Phe 660 665 670 aat ggt ctc ctt actatg tat cag agg aag agg gag cag ttt gaa aaa 2064 Asn Gly Leu Leu Thr MetTyr Gln Arg Lys Arg Glu Gln Phe Glu Lys 675 680 685 ata agc agt gct gatcct tca gga gcc ttc cgg atg ctg agc aca gcc 2112 Ile Ser Ser Ala Asp ProSer Gly Ala Phe Arg Met Leu Ser Thr Ala 690 695 700 tac gag cag tca gcccag gct gct cag cag gtc tcc gac agc tcg cgc 2160 Tyr Glu Gln Ser Ala GlnAla Ala Gln Gln Val Ser Asp Ser Ser Arg 705 710 715 720 ctt ttg gac cagctc agg gac agc cgg aga gag gca gag agg ctg gtg 2208 Leu Leu Asp Gln LeuArg Asp Ser Arg Arg Glu Ala Glu Arg Leu Val 725 730 735 cgg cag gcg ggagga gga gga ggc acc ggc agc ccc aag ctt gtg gcc 2256 Arg Gln Ala Gly GlyGly Gly Gly Thr Gly Ser Pro Lys Leu Val Ala 740 745 750 ctg agg ctg gagatg tct tcg ttg cct gac ctg aca ccc acc ttc aac 2304 Leu Arg Leu Glu MetSer Ser Leu Pro Asp Leu Thr Pro Thr Phe Asn 755 760 765 aag ctc tgt ggcaac tcc agg cag atg gct tgc acc cca ata tca tgc 2352 Lys Leu Cys Gly AsnSer Arg Gln Met Ala Cys Thr Pro Ile Ser Cys 770 775 780 cct ggt gag ctatgt ccc caa gac aat ggc aca gcc tgt ggc tcc cgc 2400 Pro Gly Glu Leu CysPro Gln Asp Asn Gly Thr Ala Cys Gly Ser Arg 785 790 795 800 tgc agg ggtgtc ctt ccc agg gcc ggt ggg gcc ttc ttg atg gcg ggg 2448 Cys Arg Gly ValLeu Pro Arg Ala Gly Gly Ala Phe Leu Met Ala Gly 805 810 815 cag gtg gctgag cag ctg cgg ggc ttc aat gcc cag ctc cag cgg acc 2496 Gln Val Ala GluGln Leu Arg Gly Phe Asn Ala Gln Leu Gln Arg Thr 820 825 830 agg cag atgatt agg gca gcc gag gaa tct gcc tca cag att caa tcc 2544 Arg Gln Met IleArg Ala Ala Glu Glu Ser Ala Ser Gln Ile Gln Ser 835 840 845 agt gcc cagcgc ttg gag acc cag gtg agc gcc agc cgc tcc cag atg 2592 Ser Ala Gln ArgLeu Glu Thr Gln Val Ser Ala Ser Arg Ser Gln Met 850 855 860 gag gaa gatgtc aga cgc aca cgg ctc cta atc cag cag gtc cgg gac 2640 Glu Glu Asp ValArg Arg Thr Arg Leu Leu Ile Gln Gln Val Arg Asp 865 870 875 880 ttc ctaaca gac ccc gac act gat gca gcc act atc cag gag gtc agc 2688 Phe Leu ThrAsp Pro Asp Thr Asp Ala Ala Thr Ile Gln Glu Val Ser 885 890 895 gag gccgtg ctg gcc ctg tgg ctg ccc aca gac tca gct act gtt ctg 2736 Glu Ala ValLeu Ala Leu Trp Leu Pro Thr Asp Ser Ala Thr Val Leu 900 905 910 cag aagatg aat gag atc cag gcc att gca gcc agg ctc ccc aac gtg 2784 Gln Lys MetAsn Glu Ile Gln Ala Ile Ala Ala Arg Leu Pro Asn Val 915 920 925 gac ttggtg ctg tcc cag acc aag cag gac att gcg cgt gcc cgc cgg 2832 Asp Leu ValLeu Ser Gln Thr Lys Gln Asp Ile Ala Arg Ala Arg Arg 930 935 940 ttg caggct gag gct gag gaa gcc agg agc cga gcc cat gca gtg gag 2880 Leu Gln AlaGlu Ala Glu Glu Ala Arg Ser Arg Ala His Ala Val Glu 945 950 955 960 ggccag gtg gaa gat gtg gtt ggg aac ctg cgg cag ggg aca gtg gca 2928 Gly GlnVal Glu Asp Val Val Gly Asn Leu Arg Gln Gly Thr Val Ala 965 970 975 ctgcag gaa gct cag gac acc atg caa ggc acc agc cgc tcc ctt cgg 2976 Leu GlnGlu Ala Gln Asp Thr Met Gln Gly Thr Ser Arg Ser Leu Arg 980 985 990 cttatc cag gac agg gtt gct gag gtt cag cag gta ctg cgg cca gca 3024 Leu IleGln Asp Arg Val Ala Glu Val Gln Gln Val Leu Arg Pro Ala 995 1000 1005gaa aag ctg gtg aca agc atg acc aag cag ctg ggt gac ttc tgg aca 3072 GluLys Leu Val Thr Ser Met Thr Lys Gln Leu Gly Asp Phe Trp Thr 1010 10151020 cgg atg gag gag ctc cgc cac caa gcc cgg cag cag ggg gca gag gca3120 Arg Met Glu Glu Leu Arg His Gln Ala Arg Gln Gln Gly Ala Glu Ala1025 1030 1035 1040 gtc cag gcc cag cag ctt gcg gaa ggt gcc agc gag caggca ttg agt 3168 Val Gln Ala Gln Gln Leu Ala Glu Gly Ala Ser Glu Gln AlaLeu Ser 1045 1050 1055 gcc caa gag gga ttt gag aga ata aaa caa aag tatgct gag ttg aag 3216 Ala Gln Glu Gly Phe Glu Arg Ile Lys Gln Lys Tyr AlaGlu Leu Lys 1060 1065 1070 gac cgg ttg ggt cag agt tcc atg ctg ggt gagcag ggt gcc cgg atc 3264 Asp Arg Leu Gly Gln Ser Ser Met Leu Gly Glu GlnGly Ala Arg Ile 1075 1080 1085 cag agt gtg aag aca gag gca gag gag ctgttt ggg gag acc atg gag 3312 Gln Ser Val Lys Thr Glu Ala Glu Glu Leu PheGly Glu Thr Met Glu 1090 1095 1100 atg atg gac agg atg aaa gac atg gagttg gag ctg ctg cgg ggc agc 3360 Met Met Asp Arg Met Lys Asp Met Glu LeuGlu Leu Leu Arg Gly Ser 1105 1110 1115 1120 cag gcc atc atg ctg cgc tcagcg gac ctg aca gga ctg gag aag cgt 3408 Gln Ala Ile Met Leu Arg Ser AlaAsp Leu Thr Gly Leu Glu Lys Arg 1125 1130 1135 gtg gag cag atc cgt gaccac atc aat ggg cgc gtg ctc tac tat gcc 3456 Val Glu Gln Ile Arg Asp HisIle Asn Gly Arg Val Leu Tyr Tyr Ala 1140 1145 1150 acc tgc aag tgat 3469Thr Cys Lys 1155 24 1155 PRT Homo sapiens 24 Gln Gln Ala Cys Ser Arg GlyAla Cys Tyr Pro Pro Val Gly Asp Leu 1 5 10 15 Leu Val Gly Arg Thr ArgPhe Leu Arg Ala Ser Ser Thr Cys Gly Leu 20 25 30 Thr Lys Pro Glu Thr TyrCys Thr Gln Tyr Gly Glu Trp Gln Met Lys 35 40 45 Cys Cys Lys Cys Asp SerArg Gln Pro His Asn Tyr Tyr Ser His Arg 50 55 60 Val Glu Asn Val Ala SerSer Ser Gly Pro Met Arg Trp Trp Gln Ser 65 70 75 80 Gln Asn Asp Val AsnPro Val Ser Leu Gln Leu Asp Leu Asp Arg Arg 85 90 95 Phe Gln Leu Gln GluVal Met Met Glu Phe Gln Gly Pro Met Pro Ala 100 105 110 Gly Met Leu IleGlu Arg Ser Ser Asp Phe Gly Lys Thr Trp Arg Val 115 120 125 Tyr Gln TyrLeu Ala Ala Asp Cys Thr Ser Thr Phe Pro Arg Val Arg 130 135 140 Gln GlyArg Pro Gln Ser Trp Gln Asp Val Arg Cys Gln Ser Leu Pro 145 150 155 160Gln Arg Pro Asn Ala Arg Leu Asn Gly Gly Lys Val Gln Leu Asn Leu 165 170175 Met Asp Leu Val Ser Gly Ile Pro Ala Thr Gln Ser Gln Lys Ile Gln 180185 190 Glu Val Gly Glu Ile Thr Asn Leu Arg Val Asn Phe Thr Arg Leu Ala195 200 205 Pro Val Pro Gln Arg Gly Tyr His Pro Pro Ser Ala Tyr Tyr AlaVal 210 215 220 Ser Gln Leu Arg Leu Gln Gly Ser Cys Phe Cys His Gly HisAla Asp 225 230 235 240 Arg Cys Ala Pro Lys Pro Gly Ala Ser Ala Gly ProSer Thr Ala Val 245 250 255 Gln Val His Asp Val Cys Val Cys Gln His AsnThr Ala Gly Pro Asn 260 265 270 Cys Glu Arg Cys Ala Pro Phe Tyr Asn AsnArg Pro Trp Arg Pro Ala 275 280 285 Glu Gly Gln Asp Ala His Glu Cys GlnArg Cys Asp Cys Asn Gly His 290 295 300 Ser Glu Thr Cys His Phe Asp ProAla Val Phe Ala Ala Ser Gln Gly 305 310 315 320 Ala Tyr Gly Gly Val CysAsp Asn Cys Arg Asp His Thr Glu Gly Lys 325 330 335 Asn Cys Glu Arg CysGln Leu His Tyr Phe Arg Asn Arg Arg Pro Gly 340 345 350 Ala Ser Ile GlnGlu Thr Cys Ile Ser Cys Glu Cys Asp Pro Asp Gly 355 360 365 Ala Val ProGly Ala Pro Cys Asp Pro Val Thr Gly Gln Cys Val Cys 370 375 380 Lys GluHis Val Gln Gly Glu Arg Cys Asp Leu Cys Lys Pro Gly Phe 385 390 395 400Thr Gly Leu Thr Tyr Ala Asn Pro Gln Gly Cys His Arg Cys Asp Cys 405 410415 Asn Ile Leu Gly Ser Arg Arg Asp Met Pro Cys Asp Glu Glu Ser Gly 420425 430 Arg Cys Leu Cys Leu Pro Asn Val Val Gly Pro Lys Cys Asp Gln Cys435 440 445 Ala Pro Tyr His Trp Lys Leu Ala Ser Gly Gln Gly Cys Glu ProCys 450 455 460 Ala Cys Asp Pro His Asn Ser Leu Ser Pro Gln Cys Asn GlnPhe Thr 465 470 475 480 Gly Gln Cys Pro Cys Arg Glu Gly Phe Gly Gly LeuMet Cys Ser Ala 485 490 495 Ala Ala Ile Arg Gln Cys Pro Asp Arg Thr TyrGly Asp Val Ala Thr 500 505 510 Gly Cys Arg Ala Cys Asp Cys Asp Phe ArgGly Thr Glu Gly Pro Gly 515 520 525 Cys Asp Lys Ala Ser Gly Arg Cys LeuCys Arg Pro Gly Leu Thr Gly 530 535 540 Pro Arg Cys Asp Gln Cys Gln ArgGly Tyr Cys Asn Arg Tyr Pro Val 545 550 555 560 Cys Val Ala Cys His ProCys Phe Gln Thr Tyr Asp Ala Asp Leu Arg 565 570 575 Glu Gln Ala Leu ArgPhe Gly Arg Leu Arg Asn Ala Thr Ala Ser Leu 580 585 590 Trp Ser Gly ProGly Leu Glu Asp Arg Gly Leu Ala Ser Arg Ile Leu 595 600 605 Asp Ala LysSer Lys Ile Glu Gln Ile Arg Ala Val Leu Ser Ser Pro 610 615 620 Ala ValThr Glu Gln Glu Val Ala Gln Val Ala Ser Ala Ile Leu Ser 625 630 635 640Leu Arg Arg Thr Leu Gln Gly Leu Gln Leu Asp Leu Pro Leu Glu Glu 645 650655 Glu Thr Leu Ser Leu Pro Arg Asp Leu Glu Ser Leu Asp Arg Ser Phe 660665 670 Asn Gly Leu Leu Thr Met Tyr Gln Arg Lys Arg Glu Gln Phe Glu Lys675 680 685 Ile Ser Ser Ala Asp Pro Ser Gly Ala Phe Arg Met Leu Ser ThrAla 690 695 700 Tyr Glu Gln Ser Ala Gln Ala Ala Gln Gln Val Ser Asp SerSer Arg 705 710 715 720 Leu Leu Asp Gln Leu Arg Asp Ser Arg Arg Glu AlaGlu Arg Leu Val 725 730 735 Arg Gln Ala Gly Gly Gly Gly Gly Thr Gly SerPro Lys Leu Val Ala 740 745 750 Leu Arg Leu Glu Met Ser Ser Leu Pro AspLeu Thr Pro Thr Phe Asn 755 760 765 Lys Leu Cys Gly Asn Ser Arg Gln MetAla Cys Thr Pro Ile Ser Cys 770 775 780 Pro Gly Glu Leu Cys Pro Gln AspAsn Gly Thr Ala Cys Gly Ser Arg 785 790 795 800 Cys Arg Gly Val Leu ProArg Ala Gly Gly Ala Phe Leu Met Ala Gly 805 810 815 Gln Val Ala Glu GlnLeu Arg Gly Phe Asn Ala Gln Leu Gln Arg Thr 820 825 830 Arg Gln Met IleArg Ala Ala Glu Glu Ser Ala Ser Gln Ile Gln Ser 835 840 845 Ser Ala GlnArg Leu Glu Thr Gln Val Ser Ala Ser Arg Ser Gln Met 850 855 860 Glu GluAsp Val Arg Arg Thr Arg Leu Leu Ile Gln Gln Val Arg Asp 865 870 875 880Phe Leu Thr Asp Pro Asp Thr Asp Ala Ala Thr Ile Gln Glu Val Ser 885 890895 Glu Ala Val Leu Ala Leu Trp Leu Pro Thr Asp Ser Ala Thr Val Leu 900905 910 Gln Lys Met Asn Glu Ile Gln Ala Ile Ala Ala Arg Leu Pro Asn Val915 920 925 Asp Leu Val Leu Ser Gln Thr Lys Gln Asp Ile Ala Arg Ala ArgArg 930 935 940 Leu Gln Ala Glu Ala Glu Glu Ala Arg Ser Arg Ala His AlaVal Glu 945 950 955 960 Gly Gln Val Glu Asp Val Val Gly Asn Leu Arg GlnGly Thr Val Ala 965 970 975 Leu Gln Glu Ala Gln Asp Thr Met Gln Gly ThrSer Arg Ser Leu Arg 980 985 990 Leu Ile Gln Asp Arg Val Ala Glu Val GlnGln Val Leu Arg Pro Ala 995 1000 1005 Glu Lys Leu Val Thr Ser Met ThrLys Gln Leu Gly Asp Phe Trp Thr 1010 1015 1020 Arg Met Glu Glu Leu ArgHis Gln Ala Arg Gln Gln Gly Ala Glu Ala 1025 1030 1035 1040 Val Gln AlaGln Gln Leu Ala Glu Gly Ala Ser Glu Gln Ala Leu Ser 1045 1050 1055 AlaGln Glu Gly Phe Glu Arg Ile Lys Gln Lys Tyr Ala Glu Leu Lys 1060 10651070 Asp Arg Leu Gly Gln Ser Ser Met Leu Gly Glu Gln Gly Ala Arg Ile1075 1080 1085 Gln Ser Val Lys Thr Glu Ala Glu Glu Leu Phe Gly Glu ThrMet Glu 1090 1095 1100 Met Met Asp Arg Met Lys Asp Met Glu Leu Glu LeuLeu Arg Gly Ser 1105 1110 1115 1120 Gln Ala Ile Met Leu Arg Ser Ala AspLeu Thr Gly Leu Glu Lys Arg 1125 1130 1135 Val Glu Gln Ile Arg Asp HisIle Asn Gly Arg Val Leu Tyr Tyr Ala 1140 1145 1150 Thr Cys Lys 1155 255200 DNA Homo sapiens CDS (118)..(3696) sig_peptide (118)..(180) 25gaccacctga tcgaaggaaa aggaaggcac agcggagcgc agagtgagaa ccaccaaccg 60aggcgccggg cagcgacccc tgcagcggag acagagactg agcggcccgg caccgcc 117 atgcct gcg ctc tgg ctg ggc tgc tgc ctc tgc ttc tcg ctc ctc ctg 165 Met ProAla Leu Trp Leu Gly Cys Cys Leu Cys Phe Ser Leu Leu Leu 1 5 10 15 cccgca gcc cgg gcc acc tcc agg agg gaa gtc tgt gat tgc aat ggg 213 Pro AlaAla Arg Ala Thr Ser Arg Arg Glu Val Cys Asp Cys Asn Gly 20 25 30 aag tccagg cag tgt atc ttt gat cgg gaa ctt cac aga caa act ggt 261 Lys Ser ArgGln Cys Ile Phe Asp Arg Glu Leu His Arg Gln Thr Gly 35 40 45 aat gga ttccgc tgc ctc aac tgc aat gac aac act gat ggc att cac 309 Asn Gly Phe ArgCys Leu Asn Cys Asn Asp Asn Thr Asp Gly Ile His 50 55 60 tgc gag aag tgcaag aat ggc ttt tac cgg cac aga gaa agg gac cgc 357 Cys Glu Lys Cys LysAsn Gly Phe Tyr Arg His Arg Glu Arg Asp Arg 65 70 75 80 tgt ttg ccc tgcaat tgt aac tcc aaa ggt tct ctt agt gct cga tgt 405 Cys Leu Pro Cys AsnCys Asn Ser Lys Gly Ser Leu Ser Ala Arg Cys 85 90 95 gac aac tct gga cggtgc agc tgt aaa cca ggt gtg aca gga gcc aga 453 Asp Asn Ser Gly Arg CysSer Cys Lys Pro Gly Val Thr Gly Ala Arg 100 105 110 tgc gac cga tgt ctgcca ggc ttc cac atg ctc acg gat gcg ggg tgc 501 Cys Asp Arg Cys Leu ProGly Phe His Met Leu Thr Asp Ala Gly Cys 115 120 125 acc caa gac cag agactg cta gac tcc aag tgt gac tgt gac cca gct 549 Thr Gln Asp Gln Arg LeuLeu Asp Ser Lys Cys Asp Cys Asp Pro Ala 130 135 140 ggc atc gca ggg ccctgt gac gcg ggc cgc tgt gtc tgc aag cca gct 597 Gly Ile Ala Gly Pro CysAsp Ala Gly Arg Cys Val Cys Lys Pro Ala 145 150 155 160 gtt act gga gaacgc tgt gat agg tgt cga tca ggt tac tat aat ctg 645 Val Thr Gly Glu ArgCys Asp Arg Cys Arg Ser Gly Tyr Tyr Asn Leu 165 170 175 gat ggg ggg aaccct gag ggc tgt acc cag tgt ttc tgc tat ggg cat 693 Asp Gly Gly Asn ProGlu Gly Cys Thr Gln Cys Phe Cys Tyr Gly His 180 185 190 tca gcc agc tgccgc agc tct gca gaa tac agt gtc cat aag atc acc 741 Ser Ala Ser Cys ArgSer Ser Ala Glu Tyr Ser Val His Lys Ile Thr 195 200 205 tct acc ttt catcaa gat gtt gat ggc tgg aag gct gtc caa cga aat 789 Ser Thr Phe His GlnAsp Val Asp Gly Trp Lys Ala Val Gln Arg Asn 210 215 220 ggg tct cct gcaaag ctc caa tgg tca cag cgc cat caa gat gtg ttt 837 Gly Ser Pro Ala LysLeu Gln Trp Ser Gln Arg His Gln Asp Val Phe 225 230 235 240 agc tca gcccaa cga cta gat cct gtc tat ttt gtg gct cct gcc aaa 885 Ser Ser Ala GlnArg Leu Asp Pro Val Tyr Phe Val Ala Pro Ala Lys 245 250 255 ttt ctt gggaat caa cag gtg agc tat ggg caa agc ctg tcc ttt gac 933 Phe Leu Gly AsnGln Gln Val Ser Tyr Gly Gln Ser Leu Ser Phe Asp 260 265 270 tac cgt gtggac aga gga ggc aga cac cca tct gcc cat gat gtg atc 981 Tyr Arg Val AspArg Gly Gly Arg His Pro Ser Ala His Asp Val Ile 275 280 285 ctg gaa ggtgct ggt cta cgg atc aca gct ccc ttg atg cca ctt ggc 1029 Leu Glu Gly AlaGly Leu Arg Ile Thr Ala Pro Leu Met Pro Leu Gly 290 295 300 aag aca ctgcct tgt ggg ctc acc aag act tac aca ttc agg tta aat 1077 Lys Thr Leu ProCys Gly Leu Thr Lys Thr Tyr Thr Phe Arg Leu Asn 305 310 315 320 gag catcca agc aat aat tgg agc ccc cag ctg agt tac ttt gag tat 1125 Glu His ProSer Asn Asn Trp Ser Pro Gln Leu Ser Tyr Phe Glu Tyr 325 330 335 cga aggtta ctg cgg aat ctc aca gcc ctc cgc atc cga gct aca tat 1173 Arg Arg LeuLeu Arg Asn Leu Thr Ala Leu Arg Ile Arg Ala Thr Tyr 340 345 350 gga gaatac agt act ggg tac att gac aat gtg acc ctg att tca gcc 1221 Gly Glu TyrSer Thr Gly Tyr Ile Asp Asn Val Thr Leu Ile Ser Ala 355 360 365 cgc cctgtc tct gga gcc cca gca ccc tgg gtt gaa cag tgt ata tgt 1269 Arg Pro ValSer Gly Ala Pro Ala Pro Trp Val Glu Gln Cys Ile Cys 370 375 380 cct gttggg tac aag ggg caa ttc tgc cag gat tgt gct tct ggc tac 1317 Pro Val GlyTyr Lys Gly Gln Phe Cys Gln Asp Cys Ala Ser Gly Tyr 385 390 395 400 aagaga gat tca gcg aga ctg ggg cct ttt ggc acc tgt att cct tgt 1365 Lys ArgAsp Ser Ala Arg Leu Gly Pro Phe Gly Thr Cys Ile Pro Cys 405 410 415 aactgt caa ggg gga ggg gcc tgt gat cca gac aca gga gat tgt tat 1413 Asn CysGln Gly Gly Gly Ala Cys Asp Pro Asp Thr Gly Asp Cys Tyr 420 425 430 tcaggg gat gag aat cct gac att gag tgt gct gac tgc cca att ggt 1461 Ser GlyAsp Glu Asn Pro Asp Ile Glu Cys Ala Asp Cys Pro Ile Gly 435 440 445 ttctac aac gat ccg cac gac ccc cgc agc tgc aag cca tgt ccc tgt 1509 Phe TyrAsn Asp Pro His Asp Pro Arg Ser Cys Lys Pro Cys Pro Cys 450 455 460 cataac ggg ttc agc tgc tca gtg att ccg gag acg gag gag gtg gtg 1557 His AsnGly Phe Ser Cys Ser Val Ile Pro Glu Thr Glu Glu Val Val 465 470 475 480tgc aat aac tgc cct ccc ggg gtc acc ggt gcc cgc tgt gag ctc tgt 1605 CysAsn Asn Cys Pro Pro Gly Val Thr Gly Ala Arg Cys Glu Leu Cys 485 490 495gct gat ggc tac ttt ggg gac ccc ttt ggt gaa cat ggc cca gtg agg 1653 AlaAsp Gly Tyr Phe Gly Asp Pro Phe Gly Glu His Gly Pro Val Arg 500 505 510cct tgt cag ccc tgt caa tgc aac agc aat gtg gac ccc agt gcc tct 1701 ProCys Gln Pro Cys Gln Cys Asn Ser Asn Val Asp Pro Ser Ala Ser 515 520 525ggg aat tgt gac cgg ctg aca ggc agg tgt ttg aag tgt atc cac aac 1749 GlyAsn Cys Asp Arg Leu Thr Gly Arg Cys Leu Lys Cys Ile His Asn 530 535 540aca gcc ggc atc tac tgc gac cag tgc aaa gca ggc tac ttc ggg gac 1797 ThrAla Gly Ile Tyr Cys Asp Gln Cys Lys Ala Gly Tyr Phe Gly Asp 545 550 555560 cca ttg gct ccc aac cca gca gac aag tgt cga gct tgc aac tgt aac 1845Pro Leu Ala Pro Asn Pro Ala Asp Lys Cys Arg Ala Cys Asn Cys Asn 565 570575 ccc atg ggc tca gag cct gta gga tgt cga agt gat ggc acc tgt gtt 1893Pro Met Gly Ser Glu Pro Val Gly Cys Arg Ser Asp Gly Thr Cys Val 580 585590 tgc aag cca gga ttt ggt ggc ccc aac tgt gag cat gga gca ttc agc 1941Cys Lys Pro Gly Phe Gly Gly Pro Asn Cys Glu His Gly Ala Phe Ser 595 600605 tgt cca gct tgc tat aat caa gtg aag att cag atg gat cag ttt atg 1989Cys Pro Ala Cys Tyr Asn Gln Val Lys Ile Gln Met Asp Gln Phe Met 610 615620 cag cag ctt cag aga atg gag gcc ctg att tca aag gct cag ggt ggt 2037Gln Gln Leu Gln Arg Met Glu Ala Leu Ile Ser Lys Ala Gln Gly Gly 625 630635 640 gat gga gta gta cct gat aca gag ctg gaa ggc agg atg cag cag gct2085 Asp Gly Val Val Pro Asp Thr Glu Leu Glu Gly Arg Met Gln Gln Ala 645650 655 gag cag gcc ctt cag gac att ctg aga gat gcc cag att tca gaa ggt2133 Glu Gln Ala Leu Gln Asp Ile Leu Arg Asp Ala Gln Ile Ser Glu Gly 660665 670 gct agc aga tcc ctt ggt ctc cag ttg gcc aag gtg agg agc caa gag2181 Ala Ser Arg Ser Leu Gly Leu Gln Leu Ala Lys Val Arg Ser Gln Glu 675680 685 aac agc tac cag agc cgc ctg gat gac ctc aag atg act gtg gaa aga2229 Asn Ser Tyr Gln Ser Arg Leu Asp Asp Leu Lys Met Thr Val Glu Arg 690695 700 gtt cgg gct ctg gga agt cag tac cag aac cga gtt cgg gat act cac2277 Val Arg Ala Leu Gly Ser Gln Tyr Gln Asn Arg Val Arg Asp Thr His 705710 715 720 agg ctc atc act cag atg cag ctg agc ctg gca gaa agt gaa gcttcc 2325 Arg Leu Ile Thr Gln Met Gln Leu Ser Leu Ala Glu Ser Glu Ala Ser725 730 735 ttg gga aac act aac att cct gcc tca gac cac tac gtg ggg ccaaat 2373 Leu Gly Asn Thr Asn Ile Pro Ala Ser Asp His Tyr Val Gly Pro Asn740 745 750 ggc ttt aaa agt ctg gct cag gag gcc aca aga tta gca gaa agccac 2421 Gly Phe Lys Ser Leu Ala Gln Glu Ala Thr Arg Leu Ala Glu Ser His755 760 765 gtt gag tca gcc agt aac atg gag caa ctg aca agg gaa act gaggac 2469 Val Glu Ser Ala Ser Asn Met Glu Gln Leu Thr Arg Glu Thr Glu Asp770 775 780 tat tcc aaa caa gcc ctc tca ctg gtg cgc aag gcc ctg cat gaagga 2517 Tyr Ser Lys Gln Ala Leu Ser Leu Val Arg Lys Ala Leu His Glu Gly785 790 795 800 gtc gga agc gga agc ggt agc ccg gac ggt gct gtg gtg caaggg ctt 2565 Val Gly Ser Gly Ser Gly Ser Pro Asp Gly Ala Val Val Gln GlyLeu 805 810 815 gtg gaa aaa ttg gag aaa acc aag tcc ctg gcc cag cag ttgaca agg 2613 Val Glu Lys Leu Glu Lys Thr Lys Ser Leu Ala Gln Gln Leu ThrArg 820 825 830 gag gcc act caa gcg gaa att gaa gca gat agg tct tat cagcac agt 2661 Glu Ala Thr Gln Ala Glu Ile Glu Ala Asp Arg Ser Tyr Gln HisSer 835 840 845 ctc cgc ctc ctg gat tca gtg tct ccg ctt cag gga gtc agtgat cag 2709 Leu Arg Leu Leu Asp Ser Val Ser Pro Leu Gln Gly Val Ser AspGln 850 855 860 tcc ttt cag gtg gaa gaa gca aag agg atc aaa caa aaa gcggat tca 2757 Ser Phe Gln Val Glu Glu Ala Lys Arg Ile Lys Gln Lys Ala AspSer 865 870 875 880 ctc tca agc ctg gta acc agg cat atg gat gag ttc aagcgt aca caa 2805 Leu Ser Ser Leu Val Thr Arg His Met Asp Glu Phe Lys ArgThr Gln 885 890 895 aag aat ctg gga aac tgg aaa gaa gaa gca cag cag ctctta cag aat 2853 Lys Asn Leu Gly Asn Trp Lys Glu Glu Ala Gln Gln Leu LeuGln Asn 900 905 910 gga aaa agt ggg aga gag aaa tca gat cag ctg ctt tcccgt gcc aat 2901 Gly Lys Ser Gly Arg Glu Lys Ser Asp Gln Leu Leu Ser ArgAla Asn 915 920 925 ctt gct aaa agc aga gca caa gaa gca ctg agt atg ggcaat gcc act 2949 Leu Ala Lys Ser Arg Ala Gln Glu Ala Leu Ser Met Gly AsnAla Thr 930 935 940 ttt tat gaa gtt gag agc atc ctt aaa aac ctc aga gagttt gac ctg 2997 Phe Tyr Glu Val Glu Ser Ile Leu Lys Asn Leu Arg Glu PheAsp Leu 945 950 955 960 cag gtg gac aac aga aaa gca gaa gct gaa gaa gccatg aag aga ctc 3045 Gln Val Asp Asn Arg Lys Ala Glu Ala Glu Glu Ala MetLys Arg Leu 965 970 975 tcc tac atc agc cag aag gtt tca gat gcc agt gacaag acc cag caa 3093 Ser Tyr Ile Ser Gln Lys Val Ser Asp Ala Ser Asp LysThr Gln Gln 980 985 990 gca gaa aga gcc ctg ggg agc gct gct gct gat gcacag agg gca aag 3141 Ala Glu Arg Ala Leu Gly Ser Ala Ala Ala Asp Ala GlnArg Ala Lys 995 1000 1005 aat ggg gcc ggg gag gcc ctg gaa atc tcc agtgag att gaa cag gag 3189 Asn Gly Ala Gly Glu Ala Leu Glu Ile Ser Ser GluIle Glu Gln Glu 1010 1015 1020 att ggg agt ctg aac ttg gaa gcc aat gtgaca gca gat gga gcc ttg 3237 Ile Gly Ser Leu Asn Leu Glu Ala Asn Val ThrAla Asp Gly Ala Leu 1025 1030 1035 1040 gcc atg gaa aag gga ctg gcc tctctg aag agt gag atg agg gaa gtg 3285 Ala Met Glu Lys Gly Leu Ala Ser LeuLys Ser Glu Met Arg Glu Val 1045 1050 1055 gaa gga gag ctg gaa agg aaggag ctg gag ttt gac acg aat atg gat 3333 Glu Gly Glu Leu Glu Arg Lys GluLeu Glu Phe Asp Thr Asn Met Asp 1060 1065 1070 gca gta cag atg gtg attaca gaa gcc cag aag gtt gat acc aga gcc 3381 Ala Val Gln Met Val Ile ThrGlu Ala Gln Lys Val Asp Thr Arg Ala 1075 1080 1085 aag aac gct ggg gttaca atc caa gac aca ctc aac aca tta gac ggc 3429 Lys Asn Ala Gly Val ThrIle Gln Asp Thr Leu Asn Thr Leu Asp Gly 1090 1095 1100 ctc ctg cat ctgatg gac cag cct ctc agt gta gat gaa gag ggg ctg 3477 Leu Leu His Leu MetAsp Gln Pro Leu Ser Val Asp Glu Glu Gly Leu 1105 1110 1115 1120 gtc ttactg gag cag aag ctt tcc cga gcc aag acc cag atc aac agc 3525 Val Leu LeuGlu Gln Lys Leu Ser Arg Ala Lys Thr Gln Ile Asn Ser 1125 1130 1135 caactg cgg ccc atg atg tca gag ctg gaa gag agg gca cgt cag cag 3573 Gln LeuArg Pro Met Met Ser Glu Leu Glu Glu Arg Ala Arg Gln Gln 1140 1145 1150agg ggc cac ctc cat ttg ctg gag aca agc ata gat ggg att ctg gct 3621 ArgGly His Leu His Leu Leu Glu Thr Ser Ile Asp Gly Ile Leu Ala 1155 11601165 gat gtg aag aac ttg gag aac att agg gac aac ctg ccc cca ggc tgc3669 Asp Val Lys Asn Leu Glu Asn Ile Arg Asp Asn Leu Pro Pro Gly Cys1170 1175 1180 tac aat acc cag gct ctt gag caa cag tgaagctgcc ataaatattt3716 Tyr Asn Thr Gln Ala Leu Glu Gln Gln 1185 1190 ctcaactgag gttcttgggatacagatctc agggctcggg agccatgtca tgtgagtggg 3776 tgggatgggg acatttgaacatgtttaatg ggtatgctca ggtcaactga cctgacccca 3836 ttcctgatcc catggccaggtggttgtctt attgcaccat actccttgct tcctgatgct 3896 gggcatgagg cagataggcactggtgtgag aatgatcaag gatctggacc ccaaagatag 3956 actggatgga aagacaaactgcacaggcag atgtttgcct cataatagtc gtaagtggag 4016 tcctggaatt tggacaagtgctgttgggat atagtcaact tattctttga gtaatgtgac 4076 taaaggaaaa aactttgactttgcccaggc atgaaattct tcctaatgtc agaacagagt 4136 gcaacccagt cacactgtggccagtaaaat actattgcct catattgtcc tctgcaagct 4196 tcttgctgat cagagttcctcctacttaca acccagggtg tgaacatgtt ctccattttc 4256 aagctggaag aagtgagcagtgttggagtg aggacctgta aggcaggccc attcagagct 4316 atggtgcttg ctggtgcctgccaccttcaa gttctggacc tgggcatgac atcctttctt 4376 ttaatgatgc catggcaacttagagattgc atttttatta aagcatttcc taccagcaaa 4436 gcaaatgttg ggaaagtatttactttttcg gtttcaaagt gatagaaaag tgtggcttgg 4496 gcattgaaag aggtaaaattctctagattt attagtccta attcaatcct acttttcgaa 4556 caccaaaaat gatgcgcatcaatgtatttt atcttatttt ctcaatctcc tctctctttc 4616 ctccacccat aataagagaatgttcctact cacacttcag ctgggtcaca tccatccctc 4676 cattcatcct tccatccatctttccatcca ttacctccat ccatccttcc aacatatatt 4736 tattgagtac ctactgtgtgccaggggctg gtgggacagt ggtgacatag tctctgccct 4796 catagagttg attgtctagtgaggaagaca agcattttta aaaaataaat ttaaacttac 4856 aaactttgtt tgtcacaagtggtgtttatt gcaataaccg cttggtttgc aacctctttg 4916 ctcaacagaa catatgttgcaagaccctcc catgggcact gagtttggca aggatgacag 4976 agctctgggt tgtgcacatttctttgcatt ccagcgtcac tctgtgcctt ctacaactga 5036 ttgcaacaga ctgttgagttatgataacac cagtgggaat tgctggagga accagaggca 5096 cttccacctt ggctgggaagactatggtgc tgccttgctt ctgtatttcc ttggattttc 5156 ctgaaagtgt ttttaaataaagaacaattg ttagatgcca aaaa 5200 26 1193 PRT Homo sapiens 26 Met Pro AlaLeu Trp Leu Gly Cys Cys Leu Cys Phe Ser Leu Leu Leu 1 5 10 15 Pro AlaAla Arg Ala Thr Ser Arg Arg Glu Val Cys Asp Cys Asn Gly 20 25 30 Lys SerArg Gln Cys Ile Phe Asp Arg Glu Leu His Arg Gln Thr Gly 35 40 45 Asn GlyPhe Arg Cys Leu Asn Cys Asn Asp Asn Thr Asp Gly Ile His 50 55 60 Cys GluLys Cys Lys Asn Gly Phe Tyr Arg His Arg Glu Arg Asp Arg 65 70 75 80 CysLeu Pro Cys Asn Cys Asn Ser Lys Gly Ser Leu Ser Ala Arg Cys 85 90 95 AspAsn Ser Gly Arg Cys Ser Cys Lys Pro Gly Val Thr Gly Ala Arg 100 105 110Cys Asp Arg Cys Leu Pro Gly Phe His Met Leu Thr Asp Ala Gly Cys 115 120125 Thr Gln Asp Gln Arg Leu Leu Asp Ser Lys Cys Asp Cys Asp Pro Ala 130135 140 Gly Ile Ala Gly Pro Cys Asp Ala Gly Arg Cys Val Cys Lys Pro Ala145 150 155 160 Val Thr Gly Glu Arg Cys Asp Arg Cys Arg Ser Gly Tyr TyrAsn Leu 165 170 175 Asp Gly Gly Asn Pro Glu Gly Cys Thr Gln Cys Phe CysTyr Gly His 180 185 190 Ser Ala Ser Cys Arg Ser Ser Ala Glu Tyr Ser ValHis Lys Ile Thr 195 200 205 Ser Thr Phe His Gln Asp Val Asp Gly Trp LysAla Val Gln Arg Asn 210 215 220 Gly Ser Pro Ala Lys Leu Gln Trp Ser GlnArg His Gln Asp Val Phe 225 230 235 240 Ser Ser Ala Gln Arg Leu Asp ProVal Tyr Phe Val Ala Pro Ala Lys 245 250 255 Phe Leu Gly Asn Gln Gln ValSer Tyr Gly Gln Ser Leu Ser Phe Asp 260 265 270 Tyr Arg Val Asp Arg GlyGly Arg His Pro Ser Ala His Asp Val Ile 275 280 285 Leu Glu Gly Ala GlyLeu Arg Ile Thr Ala Pro Leu Met Pro Leu Gly 290 295 300 Lys Thr Leu ProCys Gly Leu Thr Lys Thr Tyr Thr Phe Arg Leu Asn 305 310 315 320 Glu HisPro Ser Asn Asn Trp Ser Pro Gln Leu Ser Tyr Phe Glu Tyr 325 330 335 ArgArg Leu Leu Arg Asn Leu Thr Ala Leu Arg Ile Arg Ala Thr Tyr 340 345 350Gly Glu Tyr Ser Thr Gly Tyr Ile Asp Asn Val Thr Leu Ile Ser Ala 355 360365 Arg Pro Val Ser Gly Ala Pro Ala Pro Trp Val Glu Gln Cys Ile Cys 370375 380 Pro Val Gly Tyr Lys Gly Gln Phe Cys Gln Asp Cys Ala Ser Gly Tyr385 390 395 400 Lys Arg Asp Ser Ala Arg Leu Gly Pro Phe Gly Thr Cys IlePro Cys 405 410 415 Asn Cys Gln Gly Gly Gly Ala Cys Asp Pro Asp Thr GlyAsp Cys Tyr 420 425 430 Ser Gly Asp Glu Asn Pro Asp Ile Glu Cys Ala AspCys Pro Ile Gly 435 440 445 Phe Tyr Asn Asp Pro His Asp Pro Arg Ser CysLys Pro Cys Pro Cys 450 455 460 His Asn Gly Phe Ser Cys Ser Val Ile ProGlu Thr Glu Glu Val Val 465 470 475 480 Cys Asn Asn Cys Pro Pro Gly ValThr Gly Ala Arg Cys Glu Leu Cys 485 490 495 Ala Asp Gly Tyr Phe Gly AspPro Phe Gly Glu His Gly Pro Val Arg 500 505 510 Pro Cys Gln Pro Cys GlnCys Asn Ser Asn Val Asp Pro Ser Ala Ser 515 520 525 Gly Asn Cys Asp ArgLeu Thr Gly Arg Cys Leu Lys Cys Ile His Asn 530 535 540 Thr Ala Gly IleTyr Cys Asp Gln Cys Lys Ala Gly Tyr Phe Gly Asp 545 550 555 560 Pro LeuAla Pro Asn Pro Ala Asp Lys Cys Arg Ala Cys Asn Cys Asn 565 570 575 ProMet Gly Ser Glu Pro Val Gly Cys Arg Ser Asp Gly Thr Cys Val 580 585 590Cys Lys Pro Gly Phe Gly Gly Pro Asn Cys Glu His Gly Ala Phe Ser 595 600605 Cys Pro Ala Cys Tyr Asn Gln Val Lys Ile Gln Met Asp Gln Phe Met 610615 620 Gln Gln Leu Gln Arg Met Glu Ala Leu Ile Ser Lys Ala Gln Gly Gly625 630 635 640 Asp Gly Val Val Pro Asp Thr Glu Leu Glu Gly Arg Met GlnGln Ala 645 650 655 Glu Gln Ala Leu Gln Asp Ile Leu Arg Asp Ala Gln IleSer Glu Gly 660 665 670 Ala Ser Arg Ser Leu Gly Leu Gln Leu Ala Lys ValArg Ser Gln Glu 675 680 685 Asn Ser Tyr Gln Ser Arg Leu Asp Asp Leu LysMet Thr Val Glu Arg 690 695 700 Val Arg Ala Leu Gly Ser Gln Tyr Gln AsnArg Val Arg Asp Thr His 705 710 715 720 Arg Leu Ile Thr Gln Met Gln LeuSer Leu Ala Glu Ser Glu Ala Ser 725 730 735 Leu Gly Asn Thr Asn Ile ProAla Ser Asp His Tyr Val Gly Pro Asn 740 745 750 Gly Phe Lys Ser Leu AlaGln Glu Ala Thr Arg Leu Ala Glu Ser His 755 760 765 Val Glu Ser Ala SerAsn Met Glu Gln Leu Thr Arg Glu Thr Glu Asp 770 775 780 Tyr Ser Lys GlnAla Leu Ser Leu Val Arg Lys Ala Leu His Glu Gly 785 790 795 800 Val GlySer Gly Ser Gly Ser Pro Asp Gly Ala Val Val Gln Gly Leu 805 810 815 ValGlu Lys Leu Glu Lys Thr Lys Ser Leu Ala Gln Gln Leu Thr Arg 820 825 830Glu Ala Thr Gln Ala Glu Ile Glu Ala Asp Arg Ser Tyr Gln His Ser 835 840845 Leu Arg Leu Leu Asp Ser Val Ser Pro Leu Gln Gly Val Ser Asp Gln 850855 860 Ser Phe Gln Val Glu Glu Ala Lys Arg Ile Lys Gln Lys Ala Asp Ser865 870 875 880 Leu Ser Ser Leu Val Thr Arg His Met Asp Glu Phe Lys ArgThr Gln 885 890 895 Lys Asn Leu Gly Asn Trp Lys Glu Glu Ala Gln Gln LeuLeu Gln Asn 900 905 910 Gly Lys Ser Gly Arg Glu Lys Ser Asp Gln Leu LeuSer Arg Ala Asn 915 920 925 Leu Ala Lys Ser Arg Ala Gln Glu Ala Leu SerMet Gly Asn Ala Thr 930 935 940 Phe Tyr Glu Val Glu Ser Ile Leu Lys AsnLeu Arg Glu Phe Asp Leu 945 950 955 960 Gln Val Asp Asn Arg Lys Ala GluAla Glu Glu Ala Met Lys Arg Leu 965 970 975 Ser Tyr Ile Ser Gln Lys ValSer Asp Ala Ser Asp Lys Thr Gln Gln 980 985 990 Ala Glu Arg Ala Leu GlySer Ala Ala Ala Asp Ala Gln Arg Ala Lys 995 1000 1005 Asn Gly Ala GlyGlu Ala Leu Glu Ile Ser Ser Glu Ile Glu Gln Glu 1010 1015 1020 Ile GlySer Leu Asn Leu Glu Ala Asn Val Thr Ala Asp Gly Ala Leu 1025 1030 10351040 Ala Met Glu Lys Gly Leu Ala Ser Leu Lys Ser Glu Met Arg Glu Val1045 1050 1055 Glu Gly Glu Leu Glu Arg Lys Glu Leu Glu Phe Asp Thr AsnMet Asp 1060 1065 1070 Ala Val Gln Met Val Ile Thr Glu Ala Gln Lys ValAsp Thr Arg Ala 1075 1080 1085 Lys Asn Ala Gly Val Thr Ile Gln Asp ThrLeu Asn Thr Leu Asp Gly 1090 1095 1100 Leu Leu His Leu Met Asp Gln ProLeu Ser Val Asp Glu Glu Gly Leu 1105 1110 1115 1120 Val Leu Leu Glu GlnLys Leu Ser Arg Ala Lys Thr Gln Ile Asn Ser 1125 1130 1135 Gln Leu ArgPro Met Met Ser Glu Leu Glu Glu Arg Ala Arg Gln Gln 1140 1145 1150 ArgGly His Leu His Leu Leu Glu Thr Ser Ile Asp Gly Ile Leu Ala 1155 11601165 Asp Val Lys Asn Leu Glu Asn Ile Arg Asp Asn Leu Pro Pro Gly Cys1170 1175 1180 Tyr Asn Thr Gln Ala Leu Glu Gln Gln 1185 1190 27 5020 DNAHomo sapiens CDS (1)..(3516) 27 acc tcc agg agg gaa gtc tgt gat tgc aatggg aag tcc agg cag tgt 48 Thr Ser Arg Arg Glu Val Cys Asp Cys Asn GlyLys Ser Arg Gln Cys 1 5 10 15 atc ttt gat cgg gaa ctt cac aga caa actggt aat gga ttc cgc tgc 96 Ile Phe Asp Arg Glu Leu His Arg Gln Thr GlyAsn Gly Phe Arg Cys 20 25 30 ctc aac tgc aat gac aac act gat ggc att cactgc gag aag tgc aag 144 Leu Asn Cys Asn Asp Asn Thr Asp Gly Ile His CysGlu Lys Cys Lys 35 40 45 aat ggc ttt tac cgg cac aga gaa agg gac cgc tgtttg ccc tgc aat 192 Asn Gly Phe Tyr Arg His Arg Glu Arg Asp Arg Cys LeuPro Cys Asn 50 55 60 tgt aac tcc aaa ggt tct ctt agt gct cga tgt gac aactct gga cgg 240 Cys Asn Ser Lys Gly Ser Leu Ser Ala Arg Cys Asp Asn SerGly Arg 65 70 75 80 tgc agc tgt aaa cca ggt gtg aca gga gcc aga tgc gaccga tgt ctg 288 Cys Ser Cys Lys Pro Gly Val Thr Gly Ala Arg Cys Asp ArgCys Leu 85 90 95 cca ggc ttc cac atg ctc acg gat gcg ggg tgc acc caa gaccag aga 336 Pro Gly Phe His Met Leu Thr Asp Ala Gly Cys Thr Gln Asp GlnArg 100 105 110 ctg cta gac tcc aag tgt gac tgt gac cca gct ggc atc gcaggg ccc 384 Leu Leu Asp Ser Lys Cys Asp Cys Asp Pro Ala Gly Ile Ala GlyPro 115 120 125 tgt gac gcg ggc cgc tgt gtc tgc aag cca gct gtt act ggagaa cgc 432 Cys Asp Ala Gly Arg Cys Val Cys Lys Pro Ala Val Thr Gly GluArg 130 135 140 tgt gat agg tgt cga tca ggt tac tat aat ctg gat ggg gggaac cct 480 Cys Asp Arg Cys Arg Ser Gly Tyr Tyr Asn Leu Asp Gly Gly AsnPro 145 150 155 160 gag ggc tgt acc cag tgt ttc tgc tat ggg cat tca gccagc tgc cgc 528 Glu Gly Cys Thr Gln Cys Phe Cys Tyr Gly His Ser Ala SerCys Arg 165 170 175 agc tct gca gaa tac agt gtc cat aag atc acc tct accttt cat caa 576 Ser Ser Ala Glu Tyr Ser Val His Lys Ile Thr Ser Thr PheHis Gln 180 185 190 gat gtt gat ggc tgg aag gct gtc caa cga aat ggg tctcct gca aag 624 Asp Val Asp Gly Trp Lys Ala Val Gln Arg Asn Gly Ser ProAla Lys 195 200 205 ctc caa tgg tca cag cgc cat caa gat gtg ttt agc tcagcc caa cga 672 Leu Gln Trp Ser Gln Arg His Gln Asp Val Phe Ser Ser AlaGln Arg 210 215 220 cta gat cct gtc tat ttt gtg gct cct gcc aaa ttt cttggg aat caa 720 Leu Asp Pro Val Tyr Phe Val Ala Pro Ala Lys Phe Leu GlyAsn Gln 225 230 235 240 cag gtg agc tat ggg caa agc ctg tcc ttt gac taccgt gtg gac aga 768 Gln Val Ser Tyr Gly Gln Ser Leu Ser Phe Asp Tyr ArgVal Asp Arg 245 250 255 gga ggc aga cac cca tct gcc cat gat gtg atc ctggaa ggt gct ggt 816 Gly Gly Arg His Pro Ser Ala His Asp Val Ile Leu GluGly Ala Gly 260 265 270 cta cgg atc aca gct ccc ttg atg cca ctt ggc aagaca ctg cct tgt 864 Leu Arg Ile Thr Ala Pro Leu Met Pro Leu Gly Lys ThrLeu Pro Cys 275 280 285 ggg ctc acc aag act tac aca ttc agg tta aat gagcat cca agc aat 912 Gly Leu Thr Lys Thr Tyr Thr Phe Arg Leu Asn Glu HisPro Ser Asn 290 295 300 aat tgg agc ccc cag ctg agt tac ttt gag tat cgaagg tta ctg cgg 960 Asn Trp Ser Pro Gln Leu Ser Tyr Phe Glu Tyr Arg ArgLeu Leu Arg 305 310 315 320 aat ctc aca gcc ctc cgc atc cga gct aca tatgga gaa tac agt act 1008 Asn Leu Thr Ala Leu Arg Ile Arg Ala Thr Tyr GlyGlu Tyr Ser Thr 325 330 335 ggg tac att gac aat gtg acc ctg att tca gcccgc cct gtc tct gga 1056 Gly Tyr Ile Asp Asn Val Thr Leu Ile Ser Ala ArgPro Val Ser Gly 340 345 350 gcc cca gca ccc tgg gtt gaa cag tgt ata tgtcct gtt ggg tac aag 1104 Ala Pro Ala Pro Trp Val Glu Gln Cys Ile Cys ProVal Gly Tyr Lys 355 360 365 ggg caa ttc tgc cag gat tgt gct tct ggc tacaag aga gat tca gcg 1152 Gly Gln Phe Cys Gln Asp Cys Ala Ser Gly Tyr LysArg Asp Ser Ala 370 375 380 aga ctg ggg cct ttt ggc acc tgt att cct tgtaac tgt caa ggg gga 1200 Arg Leu Gly Pro Phe Gly Thr Cys Ile Pro Cys AsnCys Gln Gly Gly 385 390 395 400 ggg gcc tgt gat cca gac aca gga gat tgttat tca ggg gat gag aat 1248 Gly Ala Cys Asp Pro Asp Thr Gly Asp Cys TyrSer Gly Asp Glu Asn 405 410 415 cct gac att gag tgt gct gac tgc cca attggt ttc tac aac gat ccg 1296 Pro Asp Ile Glu Cys Ala Asp Cys Pro Ile GlyPhe Tyr Asn Asp Pro 420 425 430 cac gac ccc cgc agc tgc aag cca tgt ccctgt cat aac ggg ttc agc 1344 His Asp Pro Arg Ser Cys Lys Pro Cys Pro CysHis Asn Gly Phe Ser 435 440 445 tgc tca gtg att ccg gag acg gag gag gtggtg tgc aat aac tgc cct 1392 Cys Ser Val Ile Pro Glu Thr Glu Glu Val ValCys Asn Asn Cys Pro 450 455 460 ccc ggg gtc acc ggt gcc cgc tgt gag ctctgt gct gat ggc tac ttt 1440 Pro Gly Val Thr Gly Ala Arg Cys Glu Leu CysAla Asp Gly Tyr Phe 465 470 475 480 ggg gac ccc ttt ggt gaa cat ggc ccagtg agg cct tgt cag ccc tgt 1488 Gly Asp Pro Phe Gly Glu His Gly Pro ValArg Pro Cys Gln Pro Cys 485 490 495 caa tgc aac agc aat gtg gac ccc agtgcc tct ggg aat tgt gac cgg 1536 Gln Cys Asn Ser Asn Val Asp Pro Ser AlaSer Gly Asn Cys Asp Arg 500 505 510 ctg aca ggc agg tgt ttg aag tgt atccac aac aca gcc ggc atc tac 1584 Leu Thr Gly Arg Cys Leu Lys Cys Ile HisAsn Thr Ala Gly Ile Tyr 515 520 525 tgc gac cag tgc aaa gca ggc tac ttcggg gac cca ttg gct ccc aac 1632 Cys Asp Gln Cys Lys Ala Gly Tyr Phe GlyAsp Pro Leu Ala Pro Asn 530 535 540 cca gca gac aag tgt cga gct tgc aactgt aac ccc atg ggc tca gag 1680 Pro Ala Asp Lys Cys Arg Ala Cys Asn CysAsn Pro Met Gly Ser Glu 545 550 555 560 cct gta gga tgt cga agt gat ggcacc tgt gtt tgc aag cca gga ttt 1728 Pro Val Gly Cys Arg Ser Asp Gly ThrCys Val Cys Lys Pro Gly Phe 565 570 575 ggt ggc ccc aac tgt gag cat ggagca ttc agc tgt cca gct tgc tat 1776 Gly Gly Pro Asn Cys Glu His Gly AlaPhe Ser Cys Pro Ala Cys Tyr 580 585 590 aat caa gtg aag att cag atg gatcag ttt atg cag cag ctt cag aga 1824 Asn Gln Val Lys Ile Gln Met Asp GlnPhe Met Gln Gln Leu Gln Arg 595 600 605 atg gag gcc ctg att tca aag gctcag ggt ggt gat gga gta gta cct 1872 Met Glu Ala Leu Ile Ser Lys Ala GlnGly Gly Asp Gly Val Val Pro 610 615 620 gat aca gag ctg gaa ggc agg atgcag cag gct gag cag gcc ctt cag 1920 Asp Thr Glu Leu Glu Gly Arg Met GlnGln Ala Glu Gln Ala Leu Gln 625 630 635 640 gac att ctg aga gat gcc cagatt tca gaa ggt gct agc aga tcc ctt 1968 Asp Ile Leu Arg Asp Ala Gln IleSer Glu Gly Ala Ser Arg Ser Leu 645 650 655 ggt ctc cag ttg gcc aag gtgagg agc caa gag aac agc tac cag agc 2016 Gly Leu Gln Leu Ala Lys Val ArgSer Gln Glu Asn Ser Tyr Gln Ser 660 665 670 cgc ctg gat gac ctc aag atgact gtg gaa aga gtt cgg gct ctg gga 2064 Arg Leu Asp Asp Leu Lys Met ThrVal Glu Arg Val Arg Ala Leu Gly 675 680 685 agt cag tac cag aac cga gttcgg gat act cac agg ctc atc act cag 2112 Ser Gln Tyr Gln Asn Arg Val ArgAsp Thr His Arg Leu Ile Thr Gln 690 695 700 atg cag ctg agc ctg gca gaaagt gaa gct tcc ttg gga aac act aac 2160 Met Gln Leu Ser Leu Ala Glu SerGlu Ala Ser Leu Gly Asn Thr Asn 705 710 715 720 att cct gcc tca gac cactac gtg ggg cca aat ggc ttt aaa agt ctg 2208 Ile Pro Ala Ser Asp His TyrVal Gly Pro Asn Gly Phe Lys Ser Leu 725 730 735 gct cag gag gcc aca agatta gca gaa agc cac gtt gag tca gcc agt 2256 Ala Gln Glu Ala Thr Arg LeuAla Glu Ser His Val Glu Ser Ala Ser 740 745 750 aac atg gag caa ctg acaagg gaa act gag gac tat tcc aaa caa gcc 2304 Asn Met Glu Gln Leu Thr ArgGlu Thr Glu Asp Tyr Ser Lys Gln Ala 755 760 765 ctc tca ctg gtg cgc aaggcc ctg cat gaa gga gtc gga agc gga agc 2352 Leu Ser Leu Val Arg Lys AlaLeu His Glu Gly Val Gly Ser Gly Ser 770 775 780 ggt agc ccg gac ggt gctgtg gtg caa ggg ctt gtg gaa aaa ttg gag 2400 Gly Ser Pro Asp Gly Ala ValVal Gln Gly Leu Val Glu Lys Leu Glu 785 790 795 800 aaa acc aag tcc ctggcc cag cag ttg aca agg gag gcc act caa gcg 2448 Lys Thr Lys Ser Leu AlaGln Gln Leu Thr Arg Glu Ala Thr Gln Ala 805 810 815 gaa att gaa gca gatagg tct tat cag cac agt ctc cgc ctc ctg gat 2496 Glu Ile Glu Ala Asp ArgSer Tyr Gln His Ser Leu Arg Leu Leu Asp 820 825 830 tca gtg tct ccg cttcag gga gtc agt gat cag tcc ttt cag gtg gaa 2544 Ser Val Ser Pro Leu GlnGly Val Ser Asp Gln Ser Phe Gln Val Glu 835 840 845 gaa gca aag agg atcaaa caa aaa gcg gat tca ctc tca agc ctg gta 2592 Glu Ala Lys Arg Ile LysGln Lys Ala Asp Ser Leu Ser Ser Leu Val 850 855 860 acc agg cat atg gatgag ttc aag cgt aca caa aag aat ctg gga aac 2640 Thr Arg His Met Asp GluPhe Lys Arg Thr Gln Lys Asn Leu Gly Asn 865 870 875 880 tgg aaa gaa gaagca cag cag ctc tta cag aat gga aaa agt ggg aga 2688 Trp Lys Glu Glu AlaGln Gln Leu Leu Gln Asn Gly Lys Ser Gly Arg 885 890 895 gag aaa tca gatcag ctg ctt tcc cgt gcc aat ctt gct aaa agc aga 2736 Glu Lys Ser Asp GlnLeu Leu Ser Arg Ala Asn Leu Ala Lys Ser Arg 900 905 910 gca caa gaa gcactg agt atg ggc aat gcc act ttt tat gaa gtt gag 2784 Ala Gln Glu Ala LeuSer Met Gly Asn Ala Thr Phe Tyr Glu Val Glu 915 920 925 agc atc ctt aaaaac ctc aga gag ttt gac ctg cag gtg gac aac aga 2832 Ser Ile Leu Lys AsnLeu Arg Glu Phe Asp Leu Gln Val Asp Asn Arg 930 935 940 aaa gca gaa gctgaa gaa gcc atg aag aga ctc tcc tac atc agc cag 2880 Lys Ala Glu Ala GluGlu Ala Met Lys Arg Leu Ser Tyr Ile Ser Gln 945 950 955 960 aag gtt tcagat gcc agt gac aag acc cag caa gca gaa aga gcc ctg 2928 Lys Val Ser AspAla Ser Asp Lys Thr Gln Gln Ala Glu Arg Ala Leu 965 970 975 ggg agc gctgct gct gat gca cag agg gca aag aat ggg gcc ggg gag 2976 Gly Ser Ala AlaAla Asp Ala Gln Arg Ala Lys Asn Gly Ala Gly Glu 980 985 990 gcc ctg gaaatc tcc agt gag att gaa cag gag att ggg agt ctg aac 3024 Ala Leu Glu IleSer Ser Glu Ile Glu Gln Glu Ile Gly Ser Leu Asn 995 1000 1005 ttg gaagcc aat gtg aca gca gat gga gcc ttg gcc atg gaa aag gga 3072 Leu Glu AlaAsn Val Thr Ala Asp Gly Ala Leu Ala Met Glu Lys Gly 1010 1015 1020 ctggcc tct ctg aag agt gag atg agg gaa gtg gaa gga gag ctg gaa 3120 Leu AlaSer Leu Lys Ser Glu Met Arg Glu Val Glu Gly Glu Leu Glu 1025 1030 10351040 agg aag gag ctg gag ttt gac acg aat atg gat gca gta cag atg gtg3168 Arg Lys Glu Leu Glu Phe Asp Thr Asn Met Asp Ala Val Gln Met Val1045 1050 1055 att aca gaa gcc cag aag gtt gat acc aga gcc aag aac gctggg gtt 3216 Ile Thr Glu Ala Gln Lys Val Asp Thr Arg Ala Lys Asn Ala GlyVal 1060 1065 1070 aca atc caa gac aca ctc aac aca tta gac ggc ctc ctgcat ctg atg 3264 Thr Ile Gln Asp Thr Leu Asn Thr Leu Asp Gly Leu Leu HisLeu Met 1075 1080 1085 gac cag cct ctc agt gta gat gaa gag ggg ctg gtctta ctg gag cag 3312 Asp Gln Pro Leu Ser Val Asp Glu Glu Gly Leu Val LeuLeu Glu Gln 1090 1095 1100 aag ctt tcc cga gcc aag acc cag atc aac agccaa ctg cgg ccc atg 3360 Lys Leu Ser Arg Ala Lys Thr Gln Ile Asn Ser GlnLeu Arg Pro Met 1105 1110 1115 1120 atg tca gag ctg gaa gag agg gca cgtcag cag agg ggc cac ctc cat 3408 Met Ser Glu Leu Glu Glu Arg Ala Arg GlnGln Arg Gly His Leu His 1125 1130 1135 ttg ctg gag aca agc ata gat gggatt ctg gct gat gtg aag aac ttg 3456 Leu Leu Glu Thr Ser Ile Asp Gly IleLeu Ala Asp Val Lys Asn Leu 1140 1145 1150 gag aac att agg gac aac ctgccc cca ggc tgc tac aat acc cag gct 3504 Glu Asn Ile Arg Asp Asn Leu ProPro Gly Cys Tyr Asn Thr Gln Ala 1155 1160 1165 ctt gag caa cagtgaagctgcc ataaatattt ctcaactgag gttcttggga 3556 Leu Glu Gln Gln 1170tacagatctc agggctcggg agccatgtca tgtgagtggg tgggatgggg acatttgaac 3616atgtttaatg ggtatgctca ggtcaactga cctgacccca ttcctgatcc catggccagg 3676tggttgtctt attgcaccat actccttgct tcctgatgct gggcatgagg cagataggca 3736ctggtgtgag aatgatcaag gatctggacc ccaaagatag actggatgga aagacaaact 3796gcacaggcag atgtttgcct cataatagtc gtaagtggag tcctggaatt tggacaagtg 3856ctgttgggat atagtcaact tattctttga gtaatgtgac taaaggaaaa aactttgact 3916ttgcccaggc atgaaattct tcctaatgtc agaacagagt gcaacccagt cacactgtgg 3976ccagtaaaat actattgcct catattgtcc tctgcaagct tcttgctgat cagagttcct 4036cctacttaca acccagggtg tgaacatgtt ctccattttc aagctggaag aagtgagcag 4096tgttggagtg aggacctgta aggcaggccc attcagagct atggtgcttg ctggtgcctg 4156ccaccttcaa gttctggacc tgggcatgac atcctttctt ttaatgatgc catggcaact 4216tagagattgc atttttatta aagcatttcc taccagcaaa gcaaatgttg ggaaagtatt 4276tactttttcg gtttcaaagt gatagaaaag tgtggcttgg gcattgaaag aggtaaaatt 4336ctctagattt attagtccta attcaatcct acttttcgaa caccaaaaat gatgcgcatc 4396aatgtatttt atcttatttt ctcaatctcc tctctctttc ctccacccat aataagagaa 4456tgttcctact cacacttcag ctgggtcaca tccatccctc cattcatcct tccatccatc 4516tttccatcca ttacctccat ccatccttcc aacatatatt tattgagtac ctactgtgtg 4576ccaggggctg gtgggacagt ggtgacatag tctctgccct catagagttg attgtctagt 4636gaggaagaca agcattttta aaaaataaat ttaaacttac aaactttgtt tgtcacaagt 4696ggtgtttatt gcaataaccg cttggtttgc aacctctttg ctcaacagaa catatgttgc 4756aagaccctcc catgggcact gagtttggca aggatgacag agctctgggt tgtgcacatt 4816tctttgcatt ccagcgtcac tctgtgcctt ctacaactga ttgcaacaga ctgttgagtt 4876atgataacac cagtgggaat tgctggagga accagaggca cttccacctt ggctgggaag 4936actatggtgc tgccttgctt ctgtatttcc ttggattttc ctgaaagtgt ttttaaataa 4996agaacaattg ttagatgcca aaaa 5020 28 1172 PRT Homo sapiens 28 Thr Ser ArgArg Glu Val Cys Asp Cys Asn Gly Lys Ser Arg Gln Cys 1 5 10 15 Ile PheAsp Arg Glu Leu His Arg Gln Thr Gly Asn Gly Phe Arg Cys 20 25 30 Leu AsnCys Asn Asp Asn Thr Asp Gly Ile His Cys Glu Lys Cys Lys 35 40 45 Asn GlyPhe Tyr Arg His Arg Glu Arg Asp Arg Cys Leu Pro Cys Asn 50 55 60 Cys AsnSer Lys Gly Ser Leu Ser Ala Arg Cys Asp Asn Ser Gly Arg 65 70 75 80 CysSer Cys Lys Pro Gly Val Thr Gly Ala Arg Cys Asp Arg Cys Leu 85 90 95 ProGly Phe His Met Leu Thr Asp Ala Gly Cys Thr Gln Asp Gln Arg 100 105 110Leu Leu Asp Ser Lys Cys Asp Cys Asp Pro Ala Gly Ile Ala Gly Pro 115 120125 Cys Asp Ala Gly Arg Cys Val Cys Lys Pro Ala Val Thr Gly Glu Arg 130135 140 Cys Asp Arg Cys Arg Ser Gly Tyr Tyr Asn Leu Asp Gly Gly Asn Pro145 150 155 160 Glu Gly Cys Thr Gln Cys Phe Cys Tyr Gly His Ser Ala SerCys Arg 165 170 175 Ser Ser Ala Glu Tyr Ser Val His Lys Ile Thr Ser ThrPhe His Gln 180 185 190 Asp Val Asp Gly Trp Lys Ala Val Gln Arg Asn GlySer Pro Ala Lys 195 200 205 Leu Gln Trp Ser Gln Arg His Gln Asp Val PheSer Ser Ala Gln Arg 210 215 220 Leu Asp Pro Val Tyr Phe Val Ala Pro AlaLys Phe Leu Gly Asn Gln 225 230 235 240 Gln Val Ser Tyr Gly Gln Ser LeuSer Phe Asp Tyr Arg Val Asp Arg 245 250 255 Gly Gly Arg His Pro Ser AlaHis Asp Val Ile Leu Glu Gly Ala Gly 260 265 270 Leu Arg Ile Thr Ala ProLeu Met Pro Leu Gly Lys Thr Leu Pro Cys 275 280 285 Gly Leu Thr Lys ThrTyr Thr Phe Arg Leu Asn Glu His Pro Ser Asn 290 295 300 Asn Trp Ser ProGln Leu Ser Tyr Phe Glu Tyr Arg Arg Leu Leu Arg 305 310 315 320 Asn LeuThr Ala Leu Arg Ile Arg Ala Thr Tyr Gly Glu Tyr Ser Thr 325 330 335 GlyTyr Ile Asp Asn Val Thr Leu Ile Ser Ala Arg Pro Val Ser Gly 340 345 350Ala Pro Ala Pro Trp Val Glu Gln Cys Ile Cys Pro Val Gly Tyr Lys 355 360365 Gly Gln Phe Cys Gln Asp Cys Ala Ser Gly Tyr Lys Arg Asp Ser Ala 370375 380 Arg Leu Gly Pro Phe Gly Thr Cys Ile Pro Cys Asn Cys Gln Gly Gly385 390 395 400 Gly Ala Cys Asp Pro Asp Thr Gly Asp Cys Tyr Ser Gly AspGlu Asn 405 410 415 Pro Asp Ile Glu Cys Ala Asp Cys Pro Ile Gly Phe TyrAsn Asp Pro 420 425 430 His Asp Pro Arg Ser Cys Lys Pro Cys Pro Cys HisAsn Gly Phe Ser 435 440 445 Cys Ser Val Ile Pro Glu Thr Glu Glu Val ValCys Asn Asn Cys Pro 450 455 460 Pro Gly Val Thr Gly Ala Arg Cys Glu LeuCys Ala Asp Gly Tyr Phe 465 470 475 480 Gly Asp Pro Phe Gly Glu His GlyPro Val Arg Pro Cys Gln Pro Cys 485 490 495 Gln Cys Asn Ser Asn Val AspPro Ser Ala Ser Gly Asn Cys Asp Arg 500 505 510 Leu Thr Gly Arg Cys LeuLys Cys Ile His Asn Thr Ala Gly Ile Tyr 515 520 525 Cys Asp Gln Cys LysAla Gly Tyr Phe Gly Asp Pro Leu Ala Pro Asn 530 535 540 Pro Ala Asp LysCys Arg Ala Cys Asn Cys Asn Pro Met Gly Ser Glu 545 550 555 560 Pro ValGly Cys Arg Ser Asp Gly Thr Cys Val Cys Lys Pro Gly Phe 565 570 575 GlyGly Pro Asn Cys Glu His Gly Ala Phe Ser Cys Pro Ala Cys Tyr 580 585 590Asn Gln Val Lys Ile Gln Met Asp Gln Phe Met Gln Gln Leu Gln Arg 595 600605 Met Glu Ala Leu Ile Ser Lys Ala Gln Gly Gly Asp Gly Val Val Pro 610615 620 Asp Thr Glu Leu Glu Gly Arg Met Gln Gln Ala Glu Gln Ala Leu Gln625 630 635 640 Asp Ile Leu Arg Asp Ala Gln Ile Ser Glu Gly Ala Ser ArgSer Leu 645 650 655 Gly Leu Gln Leu Ala Lys Val Arg Ser Gln Glu Asn SerTyr Gln Ser 660 665 670 Arg Leu Asp Asp Leu Lys Met Thr Val Glu Arg ValArg Ala Leu Gly 675 680 685 Ser Gln Tyr Gln Asn Arg Val Arg Asp Thr HisArg Leu Ile Thr Gln 690 695 700 Met Gln Leu Ser Leu Ala Glu Ser Glu AlaSer Leu Gly Asn Thr Asn 705 710 715 720 Ile Pro Ala Ser Asp His Tyr ValGly Pro Asn Gly Phe Lys Ser Leu 725 730 735 Ala Gln Glu Ala Thr Arg LeuAla Glu Ser His Val Glu Ser Ala Ser 740 745 750 Asn Met Glu Gln Leu ThrArg Glu Thr Glu Asp Tyr Ser Lys Gln Ala 755 760 765 Leu Ser Leu Val ArgLys Ala Leu His Glu Gly Val Gly Ser Gly Ser 770 775 780 Gly Ser Pro AspGly Ala Val Val Gln Gly Leu Val Glu Lys Leu Glu 785 790 795 800 Lys ThrLys Ser Leu Ala Gln Gln Leu Thr Arg Glu Ala Thr Gln Ala 805 810 815 GluIle Glu Ala Asp Arg Ser Tyr Gln His Ser Leu Arg Leu Leu Asp 820 825 830Ser Val Ser Pro Leu Gln Gly Val Ser Asp Gln Ser Phe Gln Val Glu 835 840845 Glu Ala Lys Arg Ile Lys Gln Lys Ala Asp Ser Leu Ser Ser Leu Val 850855 860 Thr Arg His Met Asp Glu Phe Lys Arg Thr Gln Lys Asn Leu Gly Asn865 870 875 880 Trp Lys Glu Glu Ala Gln Gln Leu Leu Gln Asn Gly Lys SerGly Arg 885 890 895 Glu Lys Ser Asp Gln Leu Leu Ser Arg Ala Asn Leu AlaLys Ser Arg 900 905 910 Ala Gln Glu Ala Leu Ser Met Gly Asn Ala Thr PheTyr Glu Val Glu 915 920 925 Ser Ile Leu Lys Asn Leu Arg Glu Phe Asp LeuGln Val Asp Asn Arg 930 935 940 Lys Ala Glu Ala Glu Glu Ala Met Lys ArgLeu Ser Tyr Ile Ser Gln 945 950 955 960 Lys Val Ser Asp Ala Ser Asp LysThr Gln Gln Ala Glu Arg Ala Leu 965 970 975 Gly Ser Ala Ala Ala Asp AlaGln Arg Ala Lys Asn Gly Ala Gly Glu 980 985 990 Ala Leu Glu Ile Ser SerGlu Ile Glu Gln Glu Ile Gly Ser Leu Asn 995 1000 1005 Leu Glu Ala AsnVal Thr Ala Asp Gly Ala Leu Ala Met Glu Lys Gly 1010 1015 1020 Leu AlaSer Leu Lys Ser Glu Met Arg Glu Val Glu Gly Glu Leu Glu 1025 1030 10351040 Arg Lys Glu Leu Glu Phe Asp Thr Asn Met Asp Ala Val Gln Met Val1045 1050 1055 Ile Thr Glu Ala Gln Lys Val Asp Thr Arg Ala Lys Asn AlaGly Val 1060 1065 1070 Thr Ile Gln Asp Thr Leu Asn Thr Leu Asp Gly LeuLeu His Leu Met 1075 1080 1085 Asp Gln Pro Leu Ser Val Asp Glu Glu GlyLeu Val Leu Leu Glu Gln 1090 1095 1100 Lys Leu Ser Arg Ala Lys Thr GlnIle Asn Ser Gln Leu Arg Pro Met 1105 1110 1115 1120 Met Ser Glu Leu GluGlu Arg Ala Arg Gln Gln Arg Gly His Leu His 1125 1130 1135 Leu Leu GluThr Ser Ile Asp Gly Ile Leu Ala Asp Val Lys Asn Leu 1140 1145 1150 GluAsn Ile Arg Asp Asn Leu Pro Pro Gly Cys Tyr Asn Thr Gln Ala 1155 11601165 Leu Glu Gln Gln 1170 29 3720 DNA Homo sapiens CDS (38)..(3616)sig_peptide (38)..(100) 29 gtttaaactt aagcttggta ccgagctcgg atccgcc atgcct gcg ctc tgg ctg 55 Met Pro Ala Leu Trp Leu 1 5 ggc tgc tgc ctc tgcttc tcg ctc ctc ctg ccc gca gcc cgg gcc acc 103 Gly Cys Cys Leu Cys PheSer Leu Leu Leu Pro Ala Ala Arg Ala Thr 10 15 20 tcc agg agg gaa gtc tgtgat tgc aat ggg aag tcc agg cag tgt atc 151 Ser Arg Arg Glu Val Cys AspCys Asn Gly Lys Ser Arg Gln Cys Ile 25 30 35 ttt gat cgg gaa ctt cac agacaa act ggt aat gga ttc cgc tgc ctc 199 Phe Asp Arg Glu Leu His Arg GlnThr Gly Asn Gly Phe Arg Cys Leu 40 45 50 aac tgc aat gac aac act gat ggcatt cac tgc gag aag tgc aag aat 247 Asn Cys Asn Asp Asn Thr Asp Gly IleHis Cys Glu Lys Cys Lys Asn 55 60 65 70 ggc ttt tac cgg cac aga gaa agggac cgc tgt ttg ccc tgc aat tgt 295 Gly Phe Tyr Arg His Arg Glu Arg AspArg Cys Leu Pro Cys Asn Cys 75 80 85 aac tcc aaa ggt tct ctt agt gct cgatgt gac aac tct gga cgg tgc 343 Asn Ser Lys Gly Ser Leu Ser Ala Arg CysAsp Asn Ser Gly Arg Cys 90 95 100 agc tgt aaa cca ggt gtg aca gga gccaga tgc gac cga tgt ctg cca 391 Ser Cys Lys Pro Gly Val Thr Gly Ala ArgCys Asp Arg Cys Leu Pro 105 110 115 ggc ttc cac atg ctc acg gat gcg gggtgc acc caa gac cag aga ctg 439 Gly Phe His Met Leu Thr Asp Ala Gly CysThr Gln Asp Gln Arg Leu 120 125 130 cta gac tcc aag tgt gac tgt gac ccagct ggc atc gca ggg ccc tgt 487 Leu Asp Ser Lys Cys Asp Cys Asp Pro AlaGly Ile Ala Gly Pro Cys 135 140 145 150 gac gcg ggc cgc tgt gtc tgc aagcca gct gtt act gga gaa cgc tgt 535 Asp Ala Gly Arg Cys Val Cys Lys ProAla Val Thr Gly Glu Arg Cys 155 160 165 gat ggg tgt cga tca ggt tac tataat ctg gat ggg ggg aac cct gag 583 Asp Gly Cys Arg Ser Gly Tyr Tyr AsnLeu Asp Gly Gly Asn Pro Glu 170 175 180 ggc tgt acc cag tgt ttc tgc tatggg cat tca gcc agc tgc cgc agc 631 Gly Cys Thr Gln Cys Phe Cys Tyr GlyHis Ser Ala Ser Cys Arg Ser 185 190 195 tct gca gaa tac agt gtc cat aagatc acc tct acc ttt cat caa gat 679 Ser Ala Glu Tyr Ser Val His Lys IleThr Ser Thr Phe His Gln Asp 200 205 210 gtt gat ggc tgg aag gct gtc caacga aat ggg tct cct gca aag ctc 727 Val Asp Gly Trp Lys Ala Val Gln ArgAsn Gly Ser Pro Ala Lys Leu 215 220 225 230 caa tgg tca cag cgc cat caagat gtg ttt agc tca gcc caa cga cta 775 Gln Trp Ser Gln Arg His Gln AspVal Phe Ser Ser Ala Gln Arg Leu 235 240 245 gac cct gtc tat ttt gtg gctcct gcc aaa ttt ctt ggg aat caa cag 823 Asp Pro Val Tyr Phe Val Ala ProAla Lys Phe Leu Gly Asn Gln Gln 250 255 260 gtg agc tat ggg caa agc ctgtcc ttt gac tac cgt gtg gac aga gga 871 Val Ser Tyr Gly Gln Ser Leu SerPhe Asp Tyr Arg Val Asp Arg Gly 265 270 275 ggc aga cac cca tct gcc catgat gtg att ctg gaa ggt gct ggt cta 919 Gly Arg His Pro Ser Ala His AspVal Ile Leu Glu Gly Ala Gly Leu 280 285 290 cgg atc aca gct ccc ttg atgcca ctt ggc aag aca ctg cct tgt ggg 967 Arg Ile Thr Ala Pro Leu Met ProLeu Gly Lys Thr Leu Pro Cys Gly 295 300 305 310 ctc acc aag act tac acattc agg tta aat gag cat cca agc aat aat 1015 Leu Thr Lys Thr Tyr Thr PheArg Leu Asn Glu His Pro Ser Asn Asn 315 320 325 tgg agc ccc cag ctg agttac ttt gag tat cga agg tta ctg cgg aat 1063 Trp Ser Pro Gln Leu Ser TyrPhe Glu Tyr Arg Arg Leu Leu Arg Asn 330 335 340 ctc aca gcc ctc cgc atccga gct aca tat gga gaa tac agt act ggg 1111 Leu Thr Ala Leu Arg Ile ArgAla Thr Tyr Gly Glu Tyr Ser Thr Gly 345 350 355 tac att gac aat gtg accctg att tca gcc cgc cct gtc tct gga gcc 1159 Tyr Ile Asp Asn Val Thr LeuIle Ser Ala Arg Pro Val Ser Gly Ala 360 365 370 cca gca ccc tgg gtt gaacag tgt ata tgt cct gtt ggg tac aag ggg 1207 Pro Ala Pro Trp Val Glu GlnCys Ile Cys Pro Val Gly Tyr Lys Gly 375 380 385 390 caa ttc tgc cag gattgt gct tct ggc tac aag aga gat tca gcg aga 1255 Gln Phe Cys Gln Asp CysAla Ser Gly Tyr Lys Arg Asp Ser Ala Arg 395 400 405 ctg ggg cct ttt ggcacc tgt att cct tgt aac tgt caa ggg gga ggg 1303 Leu Gly Pro Phe Gly ThrCys Ile Pro Cys Asn Cys Gln Gly Gly Gly 410 415 420 gcc tgt gat cca gacaca gga gat tgt tat tca ggg gat gag aat cct 1351 Ala Cys Asp Pro Asp ThrGly Asp Cys Tyr Ser Gly Asp Glu Asn Pro 425 430 435 gac att gag tgt gctgac tgc cca att ggt ttc tac aac gat ccg cac 1399 Asp Ile Glu Cys Ala AspCys Pro Ile Gly Phe Tyr Asn Asp Pro His 440 445 450 gac ccc cgc agc tgcaag cca tgt ccc tgt cat aac ggg ttc agc tgc 1447 Asp Pro Arg Ser Cys LysPro Cys Pro Cys His Asn Gly Phe Ser Cys 455 460 465 470 tca gtg atg ccggag acg gag gag gtg gtg tgc aat aac tgc cct ccc 1495 Ser Val Met Pro GluThr Glu Glu Val Val Cys Asn Asn Cys Pro Pro 475 480 485 ggg gtc acc ggtgcc cgc tgt gag ctc tgt gct gat ggc tac ttt ggg 1543 Gly Val Thr Gly AlaArg Cys Glu Leu Cys Ala Asp Gly Tyr Phe Gly 490 495 500 gac ccc ttt ggtgaa cat ggc cca gtg agg cct tgt cag ccc tgt caa 1591 Asp Pro Phe Gly GluHis Gly Pro Val Arg Pro Cys Gln Pro Cys Gln 505 510 515 tgc aac aac aatgtg gac ccc agt gcc tct ggg aat tgt gac cgg ctg 1639 Cys Asn Asn Asn ValAsp Pro Ser Ala Ser Gly Asn Cys Asp Arg Leu 520 525 530 aca ggc agg tgtttg aag tgt atc cac aac aca gcc ggc atc tac tgc 1687 Thr Gly Arg Cys LeuLys Cys Ile His Asn Thr Ala Gly Ile Tyr Cys 535 540 545 550 gac cag tgcaaa gca ggc tac ttc ggg gac cca ttg gct ccc aac cca 1735 Asp Gln Cys LysAla Gly Tyr Phe Gly Asp Pro Leu Ala Pro Asn Pro 555 560 565 gca gac aagtgt cga gct tgc aac tgt aac ccc atg ggc tca gag cct 1783 Ala Asp Lys CysArg Ala Cys Asn Cys Asn Pro Met Gly Ser Glu Pro 570 575 580 gta gga tgtcga agt gat ggc acc tgt gtt tgc aag cca gga ttt ggt 1831 Val Gly Cys ArgSer Asp Gly Thr Cys Val Cys Lys Pro Gly Phe Gly 585 590 595 ggc ccc aactgt gag cat gga gca ttc agc tgt cca gct tgc tat aat 1879 Gly Pro Asn CysGlu His Gly Ala Phe Ser Cys Pro Ala Cys Tyr Asn 600 605 610 caa gtg aagatt cag atg gat cag ttt atg cag cag ctt cag aga atg 1927 Gln Val Lys IleGln Met Asp Gln Phe Met Gln Gln Leu Gln Arg Met 615 620 625 630 gag gccctg att tca aag gct cag ggt ggt gat gga gta gta cct gat 1975 Glu Ala LeuIle Ser Lys Ala Gln Gly Gly Asp Gly Val Val Pro Asp 635 640 645 aca gagctg gaa ggc agg atg cag cag gct gag cag gcc ctt cag gac 2023 Thr Glu LeuGlu Gly Arg Met Gln Gln Ala Glu Gln Ala Leu Gln Asp 650 655 660 att ctgaga gat gcc cag att tca gaa ggt gct agc aga tcc ctt ggt 2071 Ile Leu ArgAsp Ala Gln Ile Ser Glu Gly Ala Ser Arg Ser Leu Gly 665 670 675 ctc cagttg gcc aag gtg agg agc caa gag aac agc tac cag agc cgc 2119 Leu Gln LeuAla Lys Val Arg Ser Gln Glu Asn Ser Tyr Gln Ser Arg 680 685 690 ctg gatgac ctc aag atg act gtg gaa aga gtt cgg gct ctg gga agt 2167 Leu Asp AspLeu Lys Met Thr Val Glu Arg Val Arg Ala Leu Gly Ser 695 700 705 710 cagtac cag aac cga gtt cgg gat act cac agg ctc atc act cag atg 2215 Gln TyrGln Asn Arg Val Arg Asp Thr His Arg Leu Ile Thr Gln Met 715 720 725 cagctg agc ctg gca gaa agt gaa gct tcc ttg gga aac act aac att 2263 Gln LeuSer Leu Ala Glu Ser Glu Ala Ser Leu Gly Asn Thr Asn Ile 730 735 740 cctgcc tca gac cac tac gtg ggg cca aat ggc ttt aaa agt ctg gct 2311 Pro AlaSer Asp His Tyr Val Gly Pro Asn Gly Phe Lys Ser Leu Ala 745 750 755 caggag gcc aca aga tta gca gaa agc cac gtt gag tca gcc agt aac 2359 Gln GluAla Thr Arg Leu Ala Glu Ser His Val Glu Ser Ala Ser Asn 760 765 770 atggag caa ctg aca agg gaa act gag gac tat tcc aaa caa gcc ctc 2407 Met GluGln Leu Thr Arg Glu Thr Glu Asp Tyr Ser Lys Gln Ala Leu 775 780 785 790tca ctg gtg cgc aag gcc ctg cat gaa gga gtc gga agc gga agc ggt 2455 SerLeu Val Arg Lys Ala Leu His Glu Gly Val Gly Ser Gly Ser Gly 795 800 805agc ccg gac ggt gct gtg gtg caa ggg ctt gtg gaa aaa ttg gag aaa 2503 SerPro Asp Gly Ala Val Val Gln Gly Leu Val Glu Lys Leu Glu Lys 810 815 820acc aag tcc ctg gcc cag cag ttg aca agg gag gcc act caa gcg gaa 2551 ThrLys Ser Leu Ala Gln Gln Leu Thr Arg Glu Ala Thr Gln Ala Glu 825 830 835att gaa gca gat agg tct tat cag cac agt ctc cgc ctc ctg gat tca 2599 IleGlu Ala Asp Arg Ser Tyr Gln His Ser Leu Arg Leu Leu Asp Ser 840 845 850gtg tct ccg ctt cag gga gtc agt gat cag tcc ttt cag gtg gaa gaa 2647 ValSer Pro Leu Gln Gly Val Ser Asp Gln Ser Phe Gln Val Glu Glu 855 860 865870 gca aag agg atc aaa caa aaa gcg gat tca ctc tca agc ctg gta acc 2695Ala Lys Arg Ile Lys Gln Lys Ala Asp Ser Leu Ser Ser Leu Val Thr 875 880885 agg cat atg gat gag ttc aag cgt aca caa aag aat ctg gga aac tgg 2743Arg His Met Asp Glu Phe Lys Arg Thr Gln Lys Asn Leu Gly Asn Trp 890 895900 aaa gaa gaa gca cag cag ctc tta cag aat gga aaa agt ggg aga gag 2791Lys Glu Glu Ala Gln Gln Leu Leu Gln Asn Gly Lys Ser Gly Arg Glu 905 910915 aaa tca gat cag ctg ctt tcc cgt gcc aat ctt gct aaa agc aga gca 2839Lys Ser Asp Gln Leu Leu Ser Arg Ala Asn Leu Ala Lys Ser Arg Ala 920 925930 caa gaa gca ctg agt atg ggc aat gcc act ttt tat gaa gtt gag agc 2887Gln Glu Ala Leu Ser Met Gly Asn Ala Thr Phe Tyr Glu Val Glu Ser 935 940945 950 atc ctt aaa aac ctc aga gag ttt gac ctg cag gtg gac aac aga aaa2935 Ile Leu Lys Asn Leu Arg Glu Phe Asp Leu Gln Val Asp Asn Arg Lys 955960 965 gca gaa gct gaa gaa gcc atg aag aga ctc tcc tac atc agc cag aag2983 Ala Glu Ala Glu Glu Ala Met Lys Arg Leu Ser Tyr Ile Ser Gln Lys 970975 980 gtt tca gat gcc agt gac aag acc cag caa gca gaa aga gcc ctg ggg3031 Val Ser Asp Ala Ser Asp Lys Thr Gln Gln Ala Glu Arg Ala Leu Gly 985990 995 agc gct gct gct gat gca cag agg gca aag aat ggg gcc ggg gag gcc3079 Ser Ala Ala Ala Asp Ala Gln Arg Ala Lys Asn Gly Ala Gly Glu Ala1000 1005 1010 ctg gaa atc tcc agt gag att gaa cag gag att ggg agt ctgaac ttg 3127 Leu Glu Ile Ser Ser Glu Ile Glu Gln Glu Ile Gly Ser Leu AsnLeu 1015 1020 1025 1030 gaa gcc aat gtg aca gca gat gga gcc ttg gcc atggaa aag gga ctg 3175 Glu Ala Asn Val Thr Ala Asp Gly Ala Leu Ala Met GluLys Gly Leu 1035 1040 1045 gcc tct ctg aag agt gag atg agg gaa gtg gaagga gag ctg gaa agg 3223 Ala Ser Leu Lys Ser Glu Met Arg Glu Val Glu GlyGlu Leu Glu Arg 1050 1055 1060 aag gag ctg gag ttt gac acg aat atg gatgca gta cag atg gtg att 3271 Lys Glu Leu Glu Phe Asp Thr Asn Met Asp AlaVal Gln Met Val Ile 1065 1070 1075 aca gaa gcc cag aag gtt gat acc agagcc aag aac gct ggg gtt aca 3319 Thr Glu Ala Gln Lys Val Asp Thr Arg AlaLys Asn Ala Gly Val Thr 1080 1085 1090 atc caa gac aca ctc aac aca ttagac ggc ctc ctg cat ctg atg gac 3367 Ile Gln Asp Thr Leu Asn Thr Leu AspGly Leu Leu His Leu Met Asp 1095 1100 1105 1110 cag cct ctc agt gta gatgaa gag ggg ctg gtc tta ctg gag cag aag 3415 Gln Pro Leu Ser Val Asp GluGlu Gly Leu Val Leu Leu Glu Gln Lys 1115 1120 1125 ctt tcc cga gcc aagacc cag atc aac agc caa ctg cgg ccc atg atg 3463 Leu Ser Arg Ala Lys ThrGln Ile Asn Ser Gln Leu Arg Pro Met Met 1130 1135 1140 tca gag ctg gaagag agg gca cgt cag cag agg ggc cac ctc cat ttg 3511 Ser Glu Leu Glu GluArg Ala Arg Gln Gln Arg Gly His Leu His Leu 1145 1150 1155 ctg gag acaagc ata gat ggg att ctg gct gat gtg aag aac ttg gag 3559 Leu Glu Thr SerIle Asp Gly Ile Leu Ala Asp Val Lys Asn Leu Glu 1160 1165 1170 aac attagg gac aac ctg ccc cca ggc tgc tac aat acc cag gct ctt 3607 Asn Ile ArgAsp Asn Leu Pro Pro Gly Cys Tyr Asn Thr Gln Ala Leu 1175 1180 1185 1190gag caa cag tgaagctgcc ataaatattt ctcaactgag gttcttggga 3656 Glu Gln Glntacagatctc agggctcggg agccatgtca tgtgagtggg tgggatgggg acatttgaac 3716atgt 3720 30 1193 PRT Homo sapiens 30 Met Pro Ala Leu Trp Leu Gly CysCys Leu Cys Phe Ser Leu Leu Leu 1 5 10 15 Pro Ala Ala Arg Ala Thr SerArg Arg Glu Val Cys Asp Cys Asn Gly 20 25 30 Lys Ser Arg Gln Cys Ile PheAsp Arg Glu Leu His Arg Gln Thr Gly 35 40 45 Asn Gly Phe Arg Cys Leu AsnCys Asn Asp Asn Thr Asp Gly Ile His 50 55 60 Cys Glu Lys Cys Lys Asn GlyPhe Tyr Arg His Arg Glu Arg Asp Arg 65 70 75 80 Cys Leu Pro Cys Asn CysAsn Ser Lys Gly Ser Leu Ser Ala Arg Cys 85 90 95 Asp Asn Ser Gly Arg CysSer Cys Lys Pro Gly Val Thr Gly Ala Arg 100 105 110 Cys Asp Arg Cys LeuPro Gly Phe His Met Leu Thr Asp Ala Gly Cys 115 120 125 Thr Gln Asp GlnArg Leu Leu Asp Ser Lys Cys Asp Cys Asp Pro Ala 130 135 140 Gly Ile AlaGly Pro Cys Asp Ala Gly Arg Cys Val Cys Lys Pro Ala 145 150 155 160 ValThr Gly Glu Arg Cys Asp Gly Cys Arg Ser Gly Tyr Tyr Asn Leu 165 170 175Asp Gly Gly Asn Pro Glu Gly Cys Thr Gln Cys Phe Cys Tyr Gly His 180 185190 Ser Ala Ser Cys Arg Ser Ser Ala Glu Tyr Ser Val His Lys Ile Thr 195200 205 Ser Thr Phe His Gln Asp Val Asp Gly Trp Lys Ala Val Gln Arg Asn210 215 220 Gly Ser Pro Ala Lys Leu Gln Trp Ser Gln Arg His Gln Asp ValPhe 225 230 235 240 Ser Ser Ala Gln Arg Leu Asp Pro Val Tyr Phe Val AlaPro Ala Lys 245 250 255 Phe Leu Gly Asn Gln Gln Val Ser Tyr Gly Gln SerLeu Ser Phe Asp 260 265 270 Tyr Arg Val Asp Arg Gly Gly Arg His Pro SerAla His Asp Val Ile 275 280 285 Leu Glu Gly Ala Gly Leu Arg Ile Thr AlaPro Leu Met Pro Leu Gly 290 295 300 Lys Thr Leu Pro Cys Gly Leu Thr LysThr Tyr Thr Phe Arg Leu Asn 305 310 315 320 Glu His Pro Ser Asn Asn TrpSer Pro Gln Leu Ser Tyr Phe Glu Tyr 325 330 335 Arg Arg Leu Leu Arg AsnLeu Thr Ala Leu Arg Ile Arg Ala Thr Tyr 340 345 350 Gly Glu Tyr Ser ThrGly Tyr Ile Asp Asn Val Thr Leu Ile Ser Ala 355 360 365 Arg Pro Val SerGly Ala Pro Ala Pro Trp Val Glu Gln Cys Ile Cys 370 375 380 Pro Val GlyTyr Lys Gly Gln Phe Cys Gln Asp Cys Ala Ser Gly Tyr 385 390 395 400 LysArg Asp Ser Ala Arg Leu Gly Pro Phe Gly Thr Cys Ile Pro Cys 405 410 415Asn Cys Gln Gly Gly Gly Ala Cys Asp Pro Asp Thr Gly Asp Cys Tyr 420 425430 Ser Gly Asp Glu Asn Pro Asp Ile Glu Cys Ala Asp Cys Pro Ile Gly 435440 445 Phe Tyr Asn Asp Pro His Asp Pro Arg Ser Cys Lys Pro Cys Pro Cys450 455 460 His Asn Gly Phe Ser Cys Ser Val Met Pro Glu Thr Glu Glu ValVal 465 470 475 480 Cys Asn Asn Cys Pro Pro Gly Val Thr Gly Ala Arg CysGlu Leu Cys 485 490 495 Ala Asp Gly Tyr Phe Gly Asp Pro Phe Gly Glu HisGly Pro Val Arg 500 505 510 Pro Cys Gln Pro Cys Gln Cys Asn Asn Asn ValAsp Pro Ser Ala Ser 515 520 525 Gly Asn Cys Asp Arg Leu Thr Gly Arg CysLeu Lys Cys Ile His Asn 530 535 540 Thr Ala Gly Ile Tyr Cys Asp Gln CysLys Ala Gly Tyr Phe Gly Asp 545 550 555 560 Pro Leu Ala Pro Asn Pro AlaAsp Lys Cys Arg Ala Cys Asn Cys Asn 565 570 575 Pro Met Gly Ser Glu ProVal Gly Cys Arg Ser Asp Gly Thr Cys Val 580 585 590 Cys Lys Pro Gly PheGly Gly Pro Asn Cys Glu His Gly Ala Phe Ser 595 600 605 Cys Pro Ala CysTyr Asn Gln Val Lys Ile Gln Met Asp Gln Phe Met 610 615 620 Gln Gln LeuGln Arg Met Glu Ala Leu Ile Ser Lys Ala Gln Gly Gly 625 630 635 640 AspGly Val Val Pro Asp Thr Glu Leu Glu Gly Arg Met Gln Gln Ala 645 650 655Glu Gln Ala Leu Gln Asp Ile Leu Arg Asp Ala Gln Ile Ser Glu Gly 660 665670 Ala Ser Arg Ser Leu Gly Leu Gln Leu Ala Lys Val Arg Ser Gln Glu 675680 685 Asn Ser Tyr Gln Ser Arg Leu Asp Asp Leu Lys Met Thr Val Glu Arg690 695 700 Val Arg Ala Leu Gly Ser Gln Tyr Gln Asn Arg Val Arg Asp ThrHis 705 710 715 720 Arg Leu Ile Thr Gln Met Gln Leu Ser Leu Ala Glu SerGlu Ala Ser 725 730 735 Leu Gly Asn Thr Asn Ile Pro Ala Ser Asp His TyrVal Gly Pro Asn 740 745 750 Gly Phe Lys Ser Leu Ala Gln Glu Ala Thr ArgLeu Ala Glu Ser His 755 760 765 Val Glu Ser Ala Ser Asn Met Glu Gln LeuThr Arg Glu Thr Glu Asp 770 775 780 Tyr Ser Lys Gln Ala Leu Ser Leu ValArg Lys Ala Leu His Glu Gly 785 790 795 800 Val Gly Ser Gly Ser Gly SerPro Asp Gly Ala Val Val Gln Gly Leu 805 810 815 Val Glu Lys Leu Glu LysThr Lys Ser Leu Ala Gln Gln Leu Thr Arg 820 825 830 Glu Ala Thr Gln AlaGlu Ile Glu Ala Asp Arg Ser Tyr Gln His Ser 835 840 845 Leu Arg Leu LeuAsp Ser Val Ser Pro Leu Gln Gly Val Ser Asp Gln 850 855 860 Ser Phe GlnVal Glu Glu Ala Lys Arg Ile Lys Gln Lys Ala Asp Ser 865 870 875 880 LeuSer Ser Leu Val Thr Arg His Met Asp Glu Phe Lys Arg Thr Gln 885 890 895Lys Asn Leu Gly Asn Trp Lys Glu Glu Ala Gln Gln Leu Leu Gln Asn 900 905910 Gly Lys Ser Gly Arg Glu Lys Ser Asp Gln Leu Leu Ser Arg Ala Asn 915920 925 Leu Ala Lys Ser Arg Ala Gln Glu Ala Leu Ser Met Gly Asn Ala Thr930 935 940 Phe Tyr Glu Val Glu Ser Ile Leu Lys Asn Leu Arg Glu Phe AspLeu 945 950 955 960 Gln Val Asp Asn Arg Lys Ala Glu Ala Glu Glu Ala MetLys Arg Leu 965 970 975 Ser Tyr Ile Ser Gln Lys Val Ser Asp Ala Ser AspLys Thr Gln Gln 980 985 990 Ala Glu Arg Ala Leu Gly Ser Ala Ala Ala AspAla Gln Arg Ala Lys 995 1000 1005 Asn Gly Ala Gly Glu Ala Leu Glu IleSer Ser Glu Ile Glu Gln Glu 1010 1015 1020 Ile Gly Ser Leu Asn Leu GluAla Asn Val Thr Ala Asp Gly Ala Leu 1025 1030 1035 1040 Ala Met Glu LysGly Leu Ala Ser Leu Lys Ser Glu Met Arg Glu Val 1045 1050 1055 Glu GlyGlu Leu Glu Arg Lys Glu Leu Glu Phe Asp Thr Asn Met Asp 1060 1065 1070Ala Val Gln Met Val Ile Thr Glu Ala Gln Lys Val Asp Thr Arg Ala 10751080 1085 Lys Asn Ala Gly Val Thr Ile Gln Asp Thr Leu Asn Thr Leu AspGly 1090 1095 1100 Leu Leu His Leu Met Asp Gln Pro Leu Ser Val Asp GluGlu Gly Leu 1105 1110 1115 1120 Val Leu Leu Glu Gln Lys Leu Ser Arg AlaLys Thr Gln Ile Asn Ser 1125 1130 1135 Gln Leu Arg Pro Met Met Ser GluLeu Glu Glu Arg Ala Arg Gln Gln 1140 1145 1150 Arg Gly His Leu His LeuLeu Glu Thr Ser Ile Asp Gly Ile Leu Ala 1155 1160 1165 Asp Val Lys AsnLeu Glu Asn Ile Arg Asp Asn Leu Pro Pro Gly Cys 1170 1175 1180 Tyr AsnThr Gln Ala Leu Glu Gln Gln 1185 1190 31 3620 DNA Homo sapiens CDS(1)..(3516) 31 acc tcc agg agg gaa gtc tgt gat tgc aat ggg aag tcc aggcag tgt 48 Thr Ser Arg Arg Glu Val Cys Asp Cys Asn Gly Lys Ser Arg GlnCys 1 5 10 15 atc ttt gat cgg gaa ctt cac aga caa act ggt aat gga ttccgc tgc 96 Ile Phe Asp Arg Glu Leu His Arg Gln Thr Gly Asn Gly Phe ArgCys 20 25 30 ctc aac tgc aat gac aac act gat ggc att cac tgc gag aag tgcaag 144 Leu Asn Cys Asn Asp Asn Thr Asp Gly Ile His Cys Glu Lys Cys Lys35 40 45 aat ggc ttt tac cgg cac aga gaa agg gac cgc tgt ttg ccc tgc aat192 Asn Gly Phe Tyr Arg His Arg Glu Arg Asp Arg Cys Leu Pro Cys Asn 5055 60 tgt aac tcc aaa ggt tct ctt agt gct cga tgt gac aac tct gga cgg240 Cys Asn Ser Lys Gly Ser Leu Ser Ala Arg Cys Asp Asn Ser Gly Arg 6570 75 80 tgc agc tgt aaa cca ggt gtg aca gga gcc aga tgc gac cga tgt ctg288 Cys Ser Cys Lys Pro Gly Val Thr Gly Ala Arg Cys Asp Arg Cys Leu 8590 95 cca ggc ttc cac atg ctc acg gat gcg ggg tgc acc caa gac cag aga336 Pro Gly Phe His Met Leu Thr Asp Ala Gly Cys Thr Gln Asp Gln Arg 100105 110 ctg cta gac tcc aag tgt gac tgt gac cca gct ggc atc gca ggg ccc384 Leu Leu Asp Ser Lys Cys Asp Cys Asp Pro Ala Gly Ile Ala Gly Pro 115120 125 tgt gac gcg ggc cgc tgt gtc tgc aag cca gct gtt act gga gaa cgc432 Cys Asp Ala Gly Arg Cys Val Cys Lys Pro Ala Val Thr Gly Glu Arg 130135 140 tgt gat ggg tgt cga tca ggt tac tat aat ctg gat ggg ggg aac cct480 Cys Asp Gly Cys Arg Ser Gly Tyr Tyr Asn Leu Asp Gly Gly Asn Pro 145150 155 160 gag ggc tgt acc cag tgt ttc tgc tat ggg cat tca gcc agc tgccgc 528 Glu Gly Cys Thr Gln Cys Phe Cys Tyr Gly His Ser Ala Ser Cys Arg165 170 175 agc tct gca gaa tac agt gtc cat aag atc acc tct acc ttt catcaa 576 Ser Ser Ala Glu Tyr Ser Val His Lys Ile Thr Ser Thr Phe His Gln180 185 190 gat gtt gat ggc tgg aag gct gtc caa cga aat ggg tct cct gcaaag 624 Asp Val Asp Gly Trp Lys Ala Val Gln Arg Asn Gly Ser Pro Ala Lys195 200 205 ctc caa tgg tca cag cgc cat caa gat gtg ttt agc tca gcc caacga 672 Leu Gln Trp Ser Gln Arg His Gln Asp Val Phe Ser Ser Ala Gln Arg210 215 220 cta gac cct gtc tat ttt gtg gct cct gcc aaa ttt ctt ggg aatcaa 720 Leu Asp Pro Val Tyr Phe Val Ala Pro Ala Lys Phe Leu Gly Asn Gln225 230 235 240 cag gtg agc tat ggg caa agc ctg tcc ttt gac tac cgt gtggac aga 768 Gln Val Ser Tyr Gly Gln Ser Leu Ser Phe Asp Tyr Arg Val AspArg 245 250 255 gga ggc aga cac cca tct gcc cat gat gtg att ctg gaa ggtgct ggt 816 Gly Gly Arg His Pro Ser Ala His Asp Val Ile Leu Glu Gly AlaGly 260 265 270 cta cgg atc aca gct ccc ttg atg cca ctt ggc aag aca ctgcct tgt 864 Leu Arg Ile Thr Ala Pro Leu Met Pro Leu Gly Lys Thr Leu ProCys 275 280 285 ggg ctc acc aag act tac aca ttc agg tta aat gag cat ccaagc aat 912 Gly Leu Thr Lys Thr Tyr Thr Phe Arg Leu Asn Glu His Pro SerAsn 290 295 300 aat tgg agc ccc cag ctg agt tac ttt gag tat cga agg ttactg cgg 960 Asn Trp Ser Pro Gln Leu Ser Tyr Phe Glu Tyr Arg Arg Leu LeuArg 305 310 315 320 aat ctc aca gcc ctc cgc atc cga gct aca tat gga gaatac agt act 1008 Asn Leu Thr Ala Leu Arg Ile Arg Ala Thr Tyr Gly Glu TyrSer Thr 325 330 335 ggg tac att gac aat gtg acc ctg att tca gcc cgc cctgtc tct gga 1056 Gly Tyr Ile Asp Asn Val Thr Leu Ile Ser Ala Arg Pro ValSer Gly 340 345 350 gcc cca gca ccc tgg gtt gaa cag tgt ata tgt cct gttggg tac aag 1104 Ala Pro Ala Pro Trp Val Glu Gln Cys Ile Cys Pro Val GlyTyr Lys 355 360 365 ggg caa ttc tgc cag gat tgt gct tct ggc tac aag agagat tca gcg 1152 Gly Gln Phe Cys Gln Asp Cys Ala Ser Gly Tyr Lys Arg AspSer Ala 370 375 380 aga ctg ggg cct ttt ggc acc tgt att cct tgt aac tgtcaa ggg gga 1200 Arg Leu Gly Pro Phe Gly Thr Cys Ile Pro Cys Asn Cys GlnGly Gly 385 390 395 400 ggg gcc tgt gat cca gac aca gga gat tgt tat tcaggg gat gag aat 1248 Gly Ala Cys Asp Pro Asp Thr Gly Asp Cys Tyr Ser GlyAsp Glu Asn 405 410 415 cct gac att gag tgt gct gac tgc cca att ggt ttctac aac gat ccg 1296 Pro Asp Ile Glu Cys Ala Asp Cys Pro Ile Gly Phe TyrAsn Asp Pro 420 425 430 cac gac ccc cgc agc tgc aag cca tgt ccc tgt cataac ggg ttc agc 1344 His Asp Pro Arg Ser Cys Lys Pro Cys Pro Cys His AsnGly Phe Ser 435 440 445 tgc tca gtg atg ccg gag acg gag gag gtg gtg tgcaat aac tgc cct 1392 Cys Ser Val Met Pro Glu Thr Glu Glu Val Val Cys AsnAsn Cys Pro 450 455 460 ccc ggg gtc acc ggt gcc cgc tgt gag ctc tgt gctgat ggc tac ttt 1440 Pro Gly Val Thr Gly Ala Arg Cys Glu Leu Cys Ala AspGly Tyr Phe 465 470 475 480 ggg gac ccc ttt ggt gaa cat ggc cca gtg aggcct tgt cag ccc tgt 1488 Gly Asp Pro Phe Gly Glu His Gly Pro Val Arg ProCys Gln Pro Cys 485 490 495 caa tgc aac aac aat gtg gac ccc agt gcc tctggg aat tgt gac cgg 1536 Gln Cys Asn Asn Asn Val Asp Pro Ser Ala Ser GlyAsn Cys Asp Arg 500 505 510 ctg aca ggc agg tgt ttg aag tgt atc cac aacaca gcc ggc atc tac 1584 Leu Thr Gly Arg Cys Leu Lys Cys Ile His Asn ThrAla Gly Ile Tyr 515 520 525 tgc gac cag tgc aaa gca ggc tac ttc ggg gaccca ttg gct ccc aac 1632 Cys Asp Gln Cys Lys Ala Gly Tyr Phe Gly Asp ProLeu Ala Pro Asn 530 535 540 cca gca gac aag tgt cga gct tgc aac tgt aacccc atg ggc tca gag 1680 Pro Ala Asp Lys Cys Arg Ala Cys Asn Cys Asn ProMet Gly Ser Glu 545 550 555 560 cct gta gga tgt cga agt gat ggc acc tgtgtt tgc aag cca gga ttt 1728 Pro Val Gly Cys Arg Ser Asp Gly Thr Cys ValCys Lys Pro Gly Phe 565 570 575 ggt ggc ccc aac tgt gag cat gga gca ttcagc tgt cca gct tgc tat 1776 Gly Gly Pro Asn Cys Glu His Gly Ala Phe SerCys Pro Ala Cys Tyr 580 585 590 aat caa gtg aag att cag atg gat cag tttatg cag cag ctt cag aga 1824 Asn Gln Val Lys Ile Gln Met Asp Gln Phe MetGln Gln Leu Gln Arg 595 600 605 atg gag gcc ctg att tca aag gct cag ggtggt gat gga gta gta cct 1872 Met Glu Ala Leu Ile Ser Lys Ala Gln Gly GlyAsp Gly Val Val Pro 610 615 620 gat aca gag ctg gaa ggc agg atg cag caggct gag cag gcc ctt cag 1920 Asp Thr Glu Leu Glu Gly Arg Met Gln Gln AlaGlu Gln Ala Leu Gln 625 630 635 640 gac att ctg aga gat gcc cag att tcagaa ggt gct agc aga tcc ctt 1968 Asp Ile Leu Arg Asp Ala Gln Ile Ser GluGly Ala Ser Arg Ser Leu 645 650 655 ggt ctc cag ttg gcc aag gtg agg agccaa gag aac agc tac cag agc 2016 Gly Leu Gln Leu Ala Lys Val Arg Ser GlnGlu Asn Ser Tyr Gln Ser 660 665 670 cgc ctg gat gac ctc aag atg act gtggaa aga gtt cgg gct ctg gga 2064 Arg Leu Asp Asp Leu Lys Met Thr Val GluArg Val Arg Ala Leu Gly 675 680 685 agt cag tac cag aac cga gtt cgg gatact cac agg ctc atc act cag 2112 Ser Gln Tyr Gln Asn Arg Val Arg Asp ThrHis Arg Leu Ile Thr Gln 690 695 700 atg cag ctg agc ctg gca gaa agt gaagct tcc ttg gga aac act aac 2160 Met Gln Leu Ser Leu Ala Glu Ser Glu AlaSer Leu Gly Asn Thr Asn 705 710 715 720 att cct gcc tca gac cac tac gtgggg cca aat ggc ttt aaa agt ctg 2208 Ile Pro Ala Ser Asp His Tyr Val GlyPro Asn Gly Phe Lys Ser Leu 725 730 735 gct cag gag gcc aca aga tta gcagaa agc cac gtt gag tca gcc agt 2256 Ala Gln Glu Ala Thr Arg Leu Ala GluSer His Val Glu Ser Ala Ser 740 745 750 aac atg gag caa ctg aca agg gaaact gag gac tat tcc aaa caa gcc 2304 Asn Met Glu Gln Leu Thr Arg Glu ThrGlu Asp Tyr Ser Lys Gln Ala 755 760 765 ctc tca ctg gtg cgc aag gcc ctgcat gaa gga gtc gga agc gga agc 2352 Leu Ser Leu Val Arg Lys Ala Leu HisGlu Gly Val Gly Ser Gly Ser 770 775 780 ggt agc ccg gac ggt gct gtg gtgcaa ggg ctt gtg gaa aaa ttg gag 2400 Gly Ser Pro Asp Gly Ala Val Val GlnGly Leu Val Glu Lys Leu Glu 785 790 795 800 aaa acc aag tcc ctg gcc cagcag ttg aca agg gag gcc act caa gcg 2448 Lys Thr Lys Ser Leu Ala Gln GlnLeu Thr Arg Glu Ala Thr Gln Ala 805 810 815 gaa att gaa gca gat agg tcttat cag cac agt ctc cgc ctc ctg gat 2496 Glu Ile Glu Ala Asp Arg Ser TyrGln His Ser Leu Arg Leu Leu Asp 820 825 830 tca gtg tct ccg ctt cag ggagtc agt gat cag tcc ttt cag gtg gaa 2544 Ser Val Ser Pro Leu Gln Gly ValSer Asp Gln Ser Phe Gln Val Glu 835 840 845 gaa gca aag agg atc aaa caaaaa gcg gat tca ctc tca agc ctg gta 2592 Glu Ala Lys Arg Ile Lys Gln LysAla Asp Ser Leu Ser Ser Leu Val 850 855 860 acc agg cat atg gat gag ttcaag cgt aca caa aag aat ctg gga aac 2640 Thr Arg His Met Asp Glu Phe LysArg Thr Gln Lys Asn Leu Gly Asn 865 870 875 880 tgg aaa gaa gaa gca cagcag ctc tta cag aat gga aaa agt ggg aga 2688 Trp Lys Glu Glu Ala Gln GlnLeu Leu Gln Asn Gly Lys Ser Gly Arg 885 890 895 gag aaa tca gat cag ctgctt tcc cgt gcc aat ctt gct aaa agc aga 2736 Glu Lys Ser Asp Gln Leu LeuSer Arg Ala Asn Leu Ala Lys Ser Arg 900 905 910 gca caa gaa gca ctg agtatg ggc aat gcc act ttt tat gaa gtt gag 2784 Ala Gln Glu Ala Leu Ser MetGly Asn Ala Thr Phe Tyr Glu Val Glu 915 920 925 agc atc ctt aaa aac ctcaga gag ttt gac ctg cag gtg gac aac aga 2832 Ser Ile Leu Lys Asn Leu ArgGlu Phe Asp Leu Gln Val Asp Asn Arg 930 935 940 aaa gca gaa gct gaa gaagcc atg aag aga ctc tcc tac atc agc cag 2880 Lys Ala Glu Ala Glu Glu AlaMet Lys Arg Leu Ser Tyr Ile Ser Gln 945 950 955 960 aag gtt tca gat gccagt gac aag acc cag caa gca gaa aga gcc ctg 2928 Lys Val Ser Asp Ala SerAsp Lys Thr Gln Gln Ala Glu Arg Ala Leu 965 970 975 ggg agc gct gct gctgat gca cag agg gca aag aat ggg gcc ggg gag 2976 Gly Ser Ala Ala Ala AspAla Gln Arg Ala Lys Asn Gly Ala Gly Glu 980 985 990 gcc ctg gaa atc tccagt gag att gaa cag gag att ggg agt ctg aac 3024 Ala Leu Glu Ile Ser SerGlu Ile Glu Gln Glu Ile Gly Ser Leu Asn 995 1000 1005 ttg gaa gcc aatgtg aca gca gat gga gcc ttg gcc atg gaa aag gga 3072 Leu Glu Ala Asn ValThr Ala Asp Gly Ala Leu Ala Met Glu Lys Gly 1010 1015 1020 ctg gcc tctctg aag agt gag atg agg gaa gtg gaa gga gag ctg gaa 3120 Leu Ala Ser LeuLys Ser Glu Met Arg Glu Val Glu Gly Glu Leu Glu 1025 1030 1035 1040 aggaag gag ctg gag ttt gac acg aat atg gat gca gta cag atg gtg 3168 Arg LysGlu Leu Glu Phe Asp Thr Asn Met Asp Ala Val Gln Met Val 1045 1050 1055att aca gaa gcc cag aag gtt gat acc aga gcc aag aac gct ggg gtt 3216 IleThr Glu Ala Gln Lys Val Asp Thr Arg Ala Lys Asn Ala Gly Val 1060 10651070 aca atc caa gac aca ctc aac aca tta gac ggc ctc ctg cat ctg atg3264 Thr Ile Gln Asp Thr Leu Asn Thr Leu Asp Gly Leu Leu His Leu Met1075 1080 1085 gac cag cct ctc agt gta gat gaa gag ggg ctg gtc tta ctggag cag 3312 Asp Gln Pro Leu Ser Val Asp Glu Glu Gly Leu Val Leu Leu GluGln 1090 1095 1100 aag ctt tcc cga gcc aag acc cag atc aac agc caa ctgcgg ccc atg 3360 Lys Leu Ser Arg Ala Lys Thr Gln Ile Asn Ser Gln Leu ArgPro Met 1105 1110 1115 1120 atg tca gag ctg gaa gag agg gca cgt cag cagagg ggc cac ctc cat 3408 Met Ser Glu Leu Glu Glu Arg Ala Arg Gln Gln ArgGly His Leu His 1125 1130 1135 ttg ctg gag aca agc ata gat ggg att ctggct gat gtg aag aac ttg 3456 Leu Leu Glu Thr Ser Ile Asp Gly Ile Leu AlaAsp Val Lys Asn Leu 1140 1145 1150 gag aac att agg gac aac ctg ccc ccaggc tgc tac aat acc cag gct 3504 Glu Asn Ile Arg Asp Asn Leu Pro Pro GlyCys Tyr Asn Thr Gln Ala 1155 1160 1165 ctt gag caa cag tgaagctgccataaatattt ctcaactgag gttcttggga 3556 Leu Glu Gln Gln 1170 tacagatctcagggctcggg agccatgtca tgtgagtggg tgggatgggg acatttgaac 3616 atgt 3620 321172 PRT Homo sapiens 32 Thr Ser Arg Arg Glu Val Cys Asp Cys Asn Gly LysSer Arg Gln Cys 1 5 10 15 Ile Phe Asp Arg Glu Leu His Arg Gln Thr GlyAsn Gly Phe Arg Cys 20 25 30 Leu Asn Cys Asn Asp Asn Thr Asp Gly Ile HisCys Glu Lys Cys Lys 35 40 45 Asn Gly Phe Tyr Arg His Arg Glu Arg Asp ArgCys Leu Pro Cys Asn 50 55 60 Cys Asn Ser Lys Gly Ser Leu Ser Ala Arg CysAsp Asn Ser Gly Arg 65 70 75 80 Cys Ser Cys Lys Pro Gly Val Thr Gly AlaArg Cys Asp Arg Cys Leu 85 90 95 Pro Gly Phe His Met Leu Thr Asp Ala GlyCys Thr Gln Asp Gln Arg 100 105 110 Leu Leu Asp Ser Lys Cys Asp Cys AspPro Ala Gly Ile Ala Gly Pro 115 120 125 Cys Asp Ala Gly Arg Cys Val CysLys Pro Ala Val Thr Gly Glu Arg 130 135 140 Cys Asp Gly Cys Arg Ser GlyTyr Tyr Asn Leu Asp Gly Gly Asn Pro 145 150 155 160 Glu Gly Cys Thr GlnCys Phe Cys Tyr Gly His Ser Ala Ser Cys Arg 165 170 175 Ser Ser Ala GluTyr Ser Val His Lys Ile Thr Ser Thr Phe His Gln 180 185 190 Asp Val AspGly Trp Lys Ala Val Gln Arg Asn Gly Ser Pro Ala Lys 195 200 205 Leu GlnTrp Ser Gln Arg His Gln Asp Val Phe Ser Ser Ala Gln Arg 210 215 220 LeuAsp Pro Val Tyr Phe Val Ala Pro Ala Lys Phe Leu Gly Asn Gln 225 230 235240 Gln Val Ser Tyr Gly Gln Ser Leu Ser Phe Asp Tyr Arg Val Asp Arg 245250 255 Gly Gly Arg His Pro Ser Ala His Asp Val Ile Leu Glu Gly Ala Gly260 265 270 Leu Arg Ile Thr Ala Pro Leu Met Pro Leu Gly Lys Thr Leu ProCys 275 280 285 Gly Leu Thr Lys Thr Tyr Thr Phe Arg Leu Asn Glu His ProSer Asn 290 295 300 Asn Trp Ser Pro Gln Leu Ser Tyr Phe Glu Tyr Arg ArgLeu Leu Arg 305 310 315 320 Asn Leu Thr Ala Leu Arg Ile Arg Ala Thr TyrGly Glu Tyr Ser Thr 325 330 335 Gly Tyr Ile Asp Asn Val Thr Leu Ile SerAla Arg Pro Val Ser Gly 340 345 350 Ala Pro Ala Pro Trp Val Glu Gln CysIle Cys Pro Val Gly Tyr Lys 355 360 365 Gly Gln Phe Cys Gln Asp Cys AlaSer Gly Tyr Lys Arg Asp Ser Ala 370 375 380 Arg Leu Gly Pro Phe Gly ThrCys Ile Pro Cys Asn Cys Gln Gly Gly 385 390 395 400 Gly Ala Cys Asp ProAsp Thr Gly Asp Cys Tyr Ser Gly Asp Glu Asn 405 410 415 Pro Asp Ile GluCys Ala Asp Cys Pro Ile Gly Phe Tyr Asn Asp Pro 420 425 430 His Asp ProArg Ser Cys Lys Pro Cys Pro Cys His Asn Gly Phe Ser 435 440 445 Cys SerVal Met Pro Glu Thr Glu Glu Val Val Cys Asn Asn Cys Pro 450 455 460 ProGly Val Thr Gly Ala Arg Cys Glu Leu Cys Ala Asp Gly Tyr Phe 465 470 475480 Gly Asp Pro Phe Gly Glu His Gly Pro Val Arg Pro Cys Gln Pro Cys 485490 495 Gln Cys Asn Asn Asn Val Asp Pro Ser Ala Ser Gly Asn Cys Asp Arg500 505 510 Leu Thr Gly Arg Cys Leu Lys Cys Ile His Asn Thr Ala Gly IleTyr 515 520 525 Cys Asp Gln Cys Lys Ala Gly Tyr Phe Gly Asp Pro Leu AlaPro Asn 530 535 540 Pro Ala Asp Lys Cys Arg Ala Cys Asn Cys Asn Pro MetGly Ser Glu 545 550 555 560 Pro Val Gly Cys Arg Ser Asp Gly Thr Cys ValCys Lys Pro Gly Phe 565 570 575 Gly Gly Pro Asn Cys Glu His Gly Ala PheSer Cys Pro Ala Cys Tyr 580 585 590 Asn Gln Val Lys Ile Gln Met Asp GlnPhe Met Gln Gln Leu Gln Arg 595 600 605 Met Glu Ala Leu Ile Ser Lys AlaGln Gly Gly Asp Gly Val Val Pro 610 615 620 Asp Thr Glu Leu Glu Gly ArgMet Gln Gln Ala Glu Gln Ala Leu Gln 625 630 635 640 Asp Ile Leu Arg AspAla Gln Ile Ser Glu Gly Ala Ser Arg Ser Leu 645 650 655 Gly Leu Gln LeuAla Lys Val Arg Ser Gln Glu Asn Ser Tyr Gln Ser 660 665 670 Arg Leu AspAsp Leu Lys Met Thr Val Glu Arg Val Arg Ala Leu Gly 675 680 685 Ser GlnTyr Gln Asn Arg Val Arg Asp Thr His Arg Leu Ile Thr Gln 690 695 700 MetGln Leu Ser Leu Ala Glu Ser Glu Ala Ser Leu Gly Asn Thr Asn 705 710 715720 Ile Pro Ala Ser Asp His Tyr Val Gly Pro Asn Gly Phe Lys Ser Leu 725730 735 Ala Gln Glu Ala Thr Arg Leu Ala Glu Ser His Val Glu Ser Ala Ser740 745 750 Asn Met Glu Gln Leu Thr Arg Glu Thr Glu Asp Tyr Ser Lys GlnAla 755 760 765 Leu Ser Leu Val Arg Lys Ala Leu His Glu Gly Val Gly SerGly Ser 770 775 780 Gly Ser Pro Asp Gly Ala Val Val Gln Gly Leu Val GluLys Leu Glu 785 790 795 800 Lys Thr Lys Ser Leu Ala Gln Gln Leu Thr ArgGlu Ala Thr Gln Ala 805 810 815 Glu Ile Glu Ala Asp Arg Ser Tyr Gln HisSer Leu Arg Leu Leu Asp 820 825 830 Ser Val Ser Pro Leu Gln Gly Val SerAsp Gln Ser Phe Gln Val Glu 835 840 845 Glu Ala Lys Arg Ile Lys Gln LysAla Asp Ser Leu Ser Ser Leu Val 850 855 860 Thr Arg His Met Asp Glu PheLys Arg Thr Gln Lys Asn Leu Gly Asn 865 870 875 880 Trp Lys Glu Glu AlaGln Gln Leu Leu Gln Asn Gly Lys Ser Gly Arg 885 890 895 Glu Lys Ser AspGln Leu Leu Ser Arg Ala Asn Leu Ala Lys Ser Arg 900 905 910 Ala Gln GluAla Leu Ser Met Gly Asn Ala Thr Phe Tyr Glu Val Glu 915 920 925 Ser IleLeu Lys Asn Leu Arg Glu Phe Asp Leu Gln Val Asp Asn Arg 930 935 940 LysAla Glu Ala Glu Glu Ala Met Lys Arg Leu Ser Tyr Ile Ser Gln 945 950 955960 Lys Val Ser Asp Ala Ser Asp Lys Thr Gln Gln Ala Glu Arg Ala Leu 965970 975 Gly Ser Ala Ala Ala Asp Ala Gln Arg Ala Lys Asn Gly Ala Gly Glu980 985 990 Ala Leu Glu Ile Ser Ser Glu Ile Glu Gln Glu Ile Gly Ser LeuAsn 995 1000 1005 Leu Glu Ala Asn Val Thr Ala Asp Gly Ala Leu Ala MetGlu Lys Gly 1010 1015 1020 Leu Ala Ser Leu Lys Ser Glu Met Arg Glu ValGlu Gly Glu Leu Glu 1025 1030 1035 1040 Arg Lys Glu Leu Glu Phe Asp ThrAsn Met Asp Ala Val Gln Met Val 1045 1050 1055 Ile Thr Glu Ala Gln LysVal Asp Thr Arg Ala Lys Asn Ala Gly Val 1060 1065 1070 Thr Ile Gln AspThr Leu Asn Thr Leu Asp Gly Leu Leu His Leu Met 1075 1080 1085 Asp GlnPro Leu Ser Val Asp Glu Glu Gly Leu Val Leu Leu Glu Gln 1090 1095 1100Lys Leu Ser Arg Ala Lys Thr Gln Ile Asn Ser Gln Leu Arg Pro Met 11051110 1115 1120 Met Ser Glu Leu Glu Glu Arg Ala Arg Gln Gln Arg Gly HisLeu His 1125 1130 1135 Leu Leu Glu Thr Ser Ile Asp Gly Ile Leu Ala AspVal Lys Asn Leu 1140 1145 1150 Glu Asn Ile Arg Asp Asn Leu Pro Pro GlyCys Tyr Asn Thr Gln Ala 1155 1160 1165 Leu Glu Gln Gln 1170 33 5159 DNAMus musculus CDS (40)..(3615) sig_peptide (40)..(102) unsure (3330) “r”can be a or g 33 tcggcacgag ggcacccgca gcgggcaggc cgcccggcc atg cct gcgctc tgg 54 Met Pro Ala Leu Trp 1 5 ctc agc tgc tgc ctc ggt gtc gcg ctcctg ctg ccc gcc agc cag gcc 102 Leu Ser Cys Cys Leu Gly Val Ala Leu LeuLeu Pro Ala Ser Gln Ala 10 15 20 acc tcc agg agg gaa gtc tgt gat tgc aatggg aag tcc agg caa tgt 150 Thr Ser Arg Arg Glu Val Cys Asp Cys Asn GlyLys Ser Arg Gln Cys 25 30 35 gtc ttt gat cag gag ctc cat cga caa gca ggcagc ggg ttc cgt tgc 198 Val Phe Asp Gln Glu Leu His Arg Gln Ala Gly SerGly Phe Arg Cys 40 45 50 ctc aac tgc aat gac aat aca gcg ggg gtt cac tgcgag cgg tcg agg 246 Leu Asn Cys Asn Asp Asn Thr Ala Gly Val His Cys GluArg Ser Arg 55 60 65 gag ggg ttt tac cag cat cag agc aag agc cgc tgc ctaccc tgc aac 294 Glu Gly Phe Tyr Gln His Gln Ser Lys Ser Arg Cys Leu ProCys Asn 70 75 80 85 tgc cac tca aag ggt tcc ctc agt gct gga tgt gac aactct gga caa 342 Cys His Ser Lys Gly Ser Leu Ser Ala Gly Cys Asp Asn SerGly Gln 90 95 100 tgc agg tgt aag cca ggt gtg aca gga caa aga tgt gaccag tgt cag 390 Cys Arg Cys Lys Pro Gly Val Thr Gly Gln Arg Cys Asp GlnCys Gln 105 110 115 cca ggc ttc cat atg ctc acc gat gct gga tgc acc cgagac cag ggg 438 Pro Gly Phe His Met Leu Thr Asp Ala Gly Cys Thr Arg AspGln Gly 120 125 130 caa cta gat tcc aag tgt gac tgt gac cca gct ggc atctct gga ccc 486 Gln Leu Asp Ser Lys Cys Asp Cys Asp Pro Ala Gly Ile SerGly Pro 135 140 145 tgt gat tct ggc cga tgt gtc tgc aaa cca gcc gtc actgga gag cgc 534 Cys Asp Ser Gly Arg Cys Val Cys Lys Pro Ala Val Thr GlyGlu Arg 150 155 160 165 tgt gat agg tgc cga cca cgt gac tat cat ctg gaccgg gca aac cct 582 Cys Asp Arg Cys Arg Pro Arg Asp Tyr His Leu Asp ArgAla Asn Pro 170 175 180 gag ggc tgt acc cag tgt ttc tgc tat ggg cat tcagcc agc tgc cac 630 Glu Gly Cys Thr Gln Cys Phe Cys Tyr Gly His Ser AlaSer Cys His 185 190 195 gcc tct gcc gac ttc agt gtc cac aaa atc act tcaact ttc agt cag 678 Ala Ser Ala Asp Phe Ser Val His Lys Ile Thr Ser ThrPhe Ser Gln 200 205 210 gat gtg gat ggt tgg aag gcg gtt cag aga aac ggggca cct gca aaa 726 Asp Val Asp Gly Trp Lys Ala Val Gln Arg Asn Gly AlaPro Ala Lys 215 220 225 ctc cac tgg tca cag cgc cat cgg gac gtg ttt agttct gcc cga aga 774 Leu His Trp Ser Gln Arg His Arg Asp Val Phe Ser SerAla Arg Arg 230 235 240 245 tca gac ccc gtc tat ttc gtg gcc cct gcc aaattc ctc ggt aac cag 822 Ser Asp Pro Val Tyr Phe Val Ala Pro Ala Lys PheLeu Gly Asn Gln 250 255 260 caa gtg agt tac ggg cag agc ctg tct ttt gactac cgc gtg gac aga 870 Gln Val Ser Tyr Gly Gln Ser Leu Ser Phe Asp TyrArg Val Asp Arg 265 270 275 gga ggt aga cag ccg tct gcc tac gat gtg atcctg gaa ggt gct ggt 918 Gly Gly Arg Gln Pro Ser Ala Tyr Asp Val Ile LeuGlu Gly Ala Gly 280 285 290 cta cag atc aga gct cct ctg atg gct cca ggcaag aca ctt cct tgt 966 Leu Gln Ile Arg Ala Pro Leu Met Ala Pro Gly LysThr Leu Pro Cys 295 300 305 ggg atc aca aag act tac aca ttc aga ctg aatgaa cat cca agc agt 1014 Gly Ile Thr Lys Thr Tyr Thr Phe Arg Leu Asn GluHis Pro Ser Ser 310 315 320 325 cac tgg agt ccc cag ctg agt tat ttc gaatat cga agg tta ctg cgg 1062 His Trp Ser Pro Gln Leu Ser Tyr Phe Glu TyrArg Arg Leu Leu Arg 330 335 340 aac ctc aca gcc ctc ctg atg atc cga gctacg tac gga gaa tat agt 1110 Asn Leu Thr Ala Leu Leu Met Ile Arg Ala ThrTyr Gly Glu Tyr Ser 345 350 355 aca ggg tac att gat aac gtg acc ctg gtttca gcc cgc cct gtc ctt 1158 Thr Gly Tyr Ile Asp Asn Val Thr Leu Val SerAla Arg Pro Val Leu 360 365 370 gga gcc cca gcc cct tgg gtt gaa cgt tgtgta tgc ctg ctg ggg tac 1206 Gly Ala Pro Ala Pro Trp Val Glu Arg Cys ValCys Leu Leu Gly Tyr 375 380 385 aag gga caa ttc tgc cag gaa tgt gct tctggt tac aaa aga gat tcg 1254 Lys Gly Gln Phe Cys Gln Glu Cys Ala Ser GlyTyr Lys Arg Asp Ser 390 395 400 405 gca aga ttg ggc gct ttt ggc gcc tgtgtt ccc tgt aac tgc caa ggg 1302 Ala Arg Leu Gly Ala Phe Gly Ala Cys ValPro Cys Asn Cys Gln Gly 410 415 420 gag ggg gcc tgt gat cca gac acg ggagat tgc tac tcg ggg gac gag 1350 Glu Gly Ala Cys Asp Pro Asp Thr Gly AspCys Tyr Ser Gly Asp Glu 425 430 435 aat cct gac att gag tgt gct gac tgtccc atc ggt ttc tac aat gac 1398 Asn Pro Asp Ile Glu Cys Ala Asp Cys ProIle Gly Phe Tyr Asn Asp 440 445 450 cca cat gac ccc cgc agc tgc aag ccatgt ccc tgt cac aat ggg ttc 1446 Pro His Asp Pro Arg Ser Cys Lys Pro CysPro Cys His Asn Gly Phe 455 460 465 agc tgt tca gtg atg cct gag aca gaggag gtg gtg tgt aac aac tgt 1494 Ser Cys Ser Val Met Pro Glu Thr Glu GluVal Val Cys Asn Asn Cys 470 475 480 485 ccc cct ggg gtc aca ggt gcc cgctgt gag ctc tgt gct gat ggc ttc 1542 Pro Pro Gly Val Thr Gly Ala Arg CysGlu Leu Cys Ala Asp Gly Phe 490 495 500 ttt ggg gat ccc ttt ggg gaa catggc cca gtg agg cct tgt caa cgc 1590 Phe Gly Asp Pro Phe Gly Glu His GlyPro Val Arg Pro Cys Gln Arg 505 510 515 tgc caa tgc aac aac aac gtg gacccc aat gcc tct ggg aac tgt gac 1638 Cys Gln Cys Asn Asn Asn Val Asp ProAsn Ala Ser Gly Asn Cys Asp 520 525 530 cag ttg aca ggc aga tgc ttg aaatgt atc tac aac acg gcc ggt gtc 1686 Gln Leu Thr Gly Arg Cys Leu Lys CysIle Tyr Asn Thr Ala Gly Val 535 540 545 tac tgt gac cag tgc aaa gca ggttac ttt gga gac cca ttg gct ccc 1734 Tyr Cys Asp Gln Cys Lys Ala Gly TyrPhe Gly Asp Pro Leu Ala Pro 550 555 560 565 aac cca gca gac aag tgt cgagct tgc aac tgc agc ccc atg ggt gcg 1782 Asn Pro Ala Asp Lys Cys Arg AlaCys Asn Cys Ser Pro Met Gly Ala 570 575 580 gag cct gga gag tgt cga ggtgat ggc agc tgt gtt tgc aag cca ggc 1830 Glu Pro Gly Glu Cys Arg Gly AspGly Ser Cys Val Cys Lys Pro Gly 585 590 595 ttt ggc gcc ttc aac tgt gatcac gca gcc cta acc agt tgt cct gct 1878 Phe Gly Ala Phe Asn Cys Asp HisAla Ala Leu Thr Ser Cys Pro Ala 600 605 610 tgc tac aat caa gtg aag attcag atg gac cag ttt acc cag cag ctc 1926 Cys Tyr Asn Gln Val Lys Ile GlnMet Asp Gln Phe Thr Gln Gln Leu 615 620 625 cag agc ctg gag gcc ctg gtttca aag gct cag ggt ggt ggt ggt ggt 1974 Gln Ser Leu Glu Ala Leu Val SerLys Ala Gln Gly Gly Gly Gly Gly 630 635 640 645 ggt aca gtc cca gtg cagctg gaa ggc agg atc gag cag gct gag cag 2022 Gly Thr Val Pro Val Gln LeuGlu Gly Arg Ile Glu Gln Ala Glu Gln 650 655 660 gcc ctt cag gac att ctggga gaa gct cag att tca gaa ggg gca atg 2070 Ala Leu Gln Asp Ile Leu GlyGlu Ala Gln Ile Ser Glu Gly Ala Met 665 670 675 aga gcc gtt gct gtc cggctg gcc aag gca agg agc caa gag aac gac 2118 Arg Ala Val Ala Val Arg LeuAla Lys Ala Arg Ser Gln Glu Asn Asp 680 685 690 tac aag acc cgc ctg gatgac ctc aag atg act gca gaa agg atc cgg 2166 Tyr Lys Thr Arg Leu Asp AspLeu Lys Met Thr Ala Glu Arg Ile Arg 695 700 705 gcc ctg ggc agt cag catcag aac aga gtt cag gat acg agc aga ctc 2214 Ala Leu Gly Ser Gln His GlnAsn Arg Val Gln Asp Thr Ser Arg Leu 710 715 720 725 atc tct cag atg cgcctg agt ctg gca gga agc gaa gct ctc ttg gaa 2262 Ile Ser Gln Met Arg LeuSer Leu Ala Gly Ser Glu Ala Leu Leu Glu 730 735 740 aac act aat atc cattct tct gag cac tac gtg ggg ccg aat gat ttt 2310 Asn Thr Asn Ile His SerSer Glu His Tyr Val Gly Pro Asn Asp Phe 745 750 755 aaa agt ctg gct caggag gct aca aga aag gca gac agc cac gct gag 2358 Lys Ser Leu Ala Gln GluAla Thr Arg Lys Ala Asp Ser His Ala Glu 760 765 770 tca gct aac gca atgaag caa cta gca agg gaa act gag gac tac tcc 2406 Ser Ala Asn Ala Met LysGln Leu Ala Arg Glu Thr Glu Asp Tyr Ser 775 780 785 aaa caa gca ctt tcattg gcc cgc aag ctc ttg agt gga gga ggc gga 2454 Lys Gln Ala Leu Ser LeuAla Arg Lys Leu Leu Ser Gly Gly Gly Gly 790 795 800 805 agt ggc tct tgggac agc tcc gtg gta caa ggt ctt atg gga aaa tta 2502 Ser Gly Ser Trp AspSer Ser Val Val Gln Gly Leu Met Gly Lys Leu 810 815 820 gag aaa acc aagtcc ctg agc cag cag ctg tca ttg gag ggc acc caa 2550 Glu Lys Thr Lys SerLeu Ser Gln Gln Leu Ser Leu Glu Gly Thr Gln 825 830 835 gcc gac att gaagct gat agg tcg tat cag cac agt ctc cgc ctc ctg 2598 Ala Asp Ile Glu AlaAsp Arg Ser Tyr Gln His Ser Leu Arg Leu Leu 840 845 850 gat tct gcc tctcag ctt cag gga gtc agt gat ctg tcc ttt cag gtg 2646 Asp Ser Ala Ser GlnLeu Gln Gly Val Ser Asp Leu Ser Phe Gln Val 855 860 865 gaa gca aag aggatc aga caa aag gct gat tct ctc tca aac ctg gtg 2694 Glu Ala Lys Arg IleArg Gln Lys Ala Asp Ser Leu Ser Asn Leu Val 870 875 880 885 acc aga caaacg gat gca ttc acg cgt gtg cga aac aat ctg ggg aac 2742 Thr Arg Gln ThrAsp Ala Phe Thr Arg Val Arg Asn Asn Leu Gly Asn 890 895 900 tgg gaa aaagaa aca cgg cag ctt tta cag act gga aag gat agg aga 2790 Trp Glu Lys GluThr Arg Gln Leu Leu Gln Thr Gly Lys Asp Arg Arg 905 910 915 cag act tcagat cag ctg ctt tcc cgt gcc aac ctt gct aaa aac aga 2838 Gln Thr Ser AspGln Leu Leu Ser Arg Ala Asn Leu Ala Lys Asn Arg 920 925 930 gcc caa gaagcg cta agt atg ggc aat gcc act ttt tat gaa gtt gag 2886 Ala Gln Glu AlaLeu Ser Met Gly Asn Ala Thr Phe Tyr Glu Val Glu 935 940 945 aac atc ctgaag aac ctc cga gag ttt gat ctg cag gtt gaa gac aga 2934 Asn Ile Leu LysAsn Leu Arg Glu Phe Asp Leu Gln Val Glu Asp Arg 950 955 960 965 aaa gcagag gct gaa gag gcc atg aag aga ctc tcc tct att agc cag 2982 Lys Ala GluAla Glu Glu Ala Met Lys Arg Leu Ser Ser Ile Ser Gln 970 975 980 aag gttgcg gat gcc agt gac aag acc cag caa gca gaa acg gcc ctg 3030 Lys Val AlaAsp Ala Ser Asp Lys Thr Gln Gln Ala Glu Thr Ala Leu 985 990 995 ggg agcgcc act gcc gac acc caa cgg gca aag aac gca gct agg gag 3078 Gly Ser AlaThr Ala Asp Thr Gln Arg Ala Lys Asn Ala Ala Arg Glu 1000 1005 1010 gccctg gag atc agc agc gag ata gag ctg gag ata ggg agt ctg aac 3126 Ala LeuGlu Ile Ser Ser Glu Ile Glu Leu Glu Ile Gly Ser Leu Asn 1015 1020 1025ttg gaa gct aat gtg aca gca gat ggg gcc ttg gcc atg gag aaa ggg 3174 LeuGlu Ala Asn Val Thr Ala Asp Gly Ala Leu Ala Met Glu Lys Gly 1030 10351040 1045 act gcc act ctg aag agc gag atg aga gag atg att gag ctg gccaga 3222 Thr Ala Thr Leu Lys Ser Glu Met Arg Glu Met Ile Glu Leu Ala Arg1050 1055 1060 aag gag ctg gag ttt gac acg gat aag gac acg gtg cag ctggtg att 3270 Lys Glu Leu Glu Phe Asp Thr Asp Lys Asp Thr Val Gln Leu ValIle 1065 1070 1075 act gaa gcc cag caa gct gat gcc aga gcc acg agt gccgga gtt acc 3318 Thr Glu Ala Gln Gln Ala Asp Ala Arg Ala Thr Ser Ala GlyVal Thr 1080 1085 1090 atc caa gac acr ctc aac aca ttg gac ggc atc ctacac ctc ata gac 3366 Ile Gln Asp Thr Leu Asn Thr Leu Asp Gly Ile Leu HisLeu Ile Asp 1095 1100 1105 cag cct ggc agt gtg gat gaa gaa ggg atg atgcta tta gaa caa ggg 3414 Gln Pro Gly Ser Val Asp Glu Glu Gly Met Met LeuLeu Glu Gln Gly 1110 1115 1120 1125 ctt ttc caa gcc aag acc cag atc aacagt cga ctt cgg ccc ttg atg 3462 Leu Phe Gln Ala Lys Thr Gln Ile Asn SerArg Leu Arg Pro Leu Met 1130 1135 1140 tct gac ctg gag gag agg gtg cgtcgg cag agg aac cac ctc cat ctg 3510 Ser Asp Leu Glu Glu Arg Val Arg ArgGln Arg Asn His Leu His Leu 1145 1150 1155 ctg gag act agc ata gat ggaatt ctt gct gat gtg aag aac ctg gag 3558 Leu Glu Thr Ser Ile Asp Gly IleLeu Ala Asp Val Lys Asn Leu Glu 1160 1165 1170 aac att cga gac aac ctgccc cca ggc tgc tac aat acc caa gct ctt 3606 Asn Ile Arg Asp Asn Leu ProPro Gly Cys Tyr Asn Thr Gln Ala Leu 1175 1180 1185 gag caa cagtgaagttgtc atagagattt gtccactgtt gtgaaaggac 3655 Glu Gln Gln 1190acagacctca ggggtcagga gccatctcgt gtggatgggc tgtgctcagg ctatctgaac 3715acatttaatg ggtttgttca ggtccaattc catccctgag accatgggct gtggatgtct 3775tcctgtacca atataatact gtttgtactt cctgatgctg gcagtgaggc agatagcatt 3835gagtatgaga ttgatcaagg agggacaaat cgtgcgctca gaacagtgac aaactgaatt 3895ctgggcagtg aggcagatag cattgagtat gagattgatc aaggacctgg accccaaaga 3955tagactggat ggaaagacaa actgcacagg cagatgtttg cctcataata gtcgtaagtg 4015gagtcctgga atttggtcag aacagtgaaa aactggaatt ctgggatata gaaagatcct 4075gctgctatgt caggacaaag tgagatctaa tcccgctgcg gccagcaaag tactcttgct 4135tcacccacta gacgtttttt gtccaccaca tttcctccag tgcccaccca atacatgagt 4195atgtcctcca cttcatgctg agtgcagaga gcagtgatgg tatagatctg gaaatctggc 4255ccatgtggag cagtggtgcc cgcctgcacc cctaaccttc atgctctcgg cctgagtgtg 4315acagcctttc tcctaatggt gcgaacaact tagaggctgt atttttttat gaaagcatct 4375tttaccagcc aagcaatcat tgggaaagta tttctttgag tttcaaagtg atataagaaa 4435tgtgtctggc actaaaggaa gtggagttat ctaaaagata tattcatcat aatccaatct 4495tcctttggaa acactaaaac tcatatacat ctgtgtattg tatcttattt tctctttctc 4555ctctctcttt cctccaccca taataagaga atgttcctac tcacacttca gctgggtcac 4615atccatccct ccattcatcc ttccatccat ctttccatcc attacctcca tccagccttc 4675taacatatat ttattgcgtc actactgtgt gccaggggtg agtggaacag tatggacagt 4735ctctactctc atggagttga gtgtctagtg agagaacaac attagaataa gtaaatggaa 4795actcccatgc cttgttcatc tcatgtgata tttattgcag tcacccaccc tttggtttga 4855aacctctttt cttaataatg tgttgcaaga cattcccatg agggtacttg agttagagca 4915aagttgagat cgctctgagt tgtacacatt tctctatgtt ccagccgtct ctccacccct 4975tccacacaga ctgtgcacag actggtgcat cagggcaata ccagtgggaa ttgctgaagg 5035aaccagaggc attgggacct cagtttggaa gactactgta ctgtctcacc tctgtacttc 5095cttgtctttt catggatgtg ttattaaata aagaacgagt gttagatgct aaaaaaaaaa 5155aaaa 5159 34 1192 PRT Mus musculus 34 Met Pro Ala Leu Trp Leu Ser CysCys Leu Gly Val Ala Leu Leu Leu 1 5 10 15 Pro Ala Ser Gln Ala Thr SerArg Arg Glu Val Cys Asp Cys Asn Gly 20 25 30 Lys Ser Arg Gln Cys Val PheAsp Gln Glu Leu His Arg Gln Ala Gly 35 40 45 Ser Gly Phe Arg Cys Leu AsnCys Asn Asp Asn Thr Ala Gly Val His 50 55 60 Cys Glu Arg Ser Arg Glu GlyPhe Tyr Gln His Gln Ser Lys Ser Arg 65 70 75 80 Cys Leu Pro Cys Asn CysHis Ser Lys Gly Ser Leu Ser Ala Gly Cys 85 90 95 Asp Asn Ser Gly Gln CysArg Cys Lys Pro Gly Val Thr Gly Gln Arg 100 105 110 Cys Asp Gln Cys GlnPro Gly Phe His Met Leu Thr Asp Ala Gly Cys 115 120 125 Thr Arg Asp GlnGly Gln Leu Asp Ser Lys Cys Asp Cys Asp Pro Ala 130 135 140 Gly Ile SerGly Pro Cys Asp Ser Gly Arg Cys Val Cys Lys Pro Ala 145 150 155 160 ValThr Gly Glu Arg Cys Asp Arg Cys Arg Pro Arg Asp Tyr His Leu 165 170 175Asp Arg Ala Asn Pro Glu Gly Cys Thr Gln Cys Phe Cys Tyr Gly His 180 185190 Ser Ala Ser Cys His Ala Ser Ala Asp Phe Ser Val His Lys Ile Thr 195200 205 Ser Thr Phe Ser Gln Asp Val Asp Gly Trp Lys Ala Val Gln Arg Asn210 215 220 Gly Ala Pro Ala Lys Leu His Trp Ser Gln Arg His Arg Asp ValPhe 225 230 235 240 Ser Ser Ala Arg Arg Ser Asp Pro Val Tyr Phe Val AlaPro Ala Lys 245 250 255 Phe Leu Gly Asn Gln Gln Val Ser Tyr Gly Gln SerLeu Ser Phe Asp 260 265 270 Tyr Arg Val Asp Arg Gly Gly Arg Gln Pro SerAla Tyr Asp Val Ile 275 280 285 Leu Glu Gly Ala Gly Leu Gln Ile Arg AlaPro Leu Met Ala Pro Gly 290 295 300 Lys Thr Leu Pro Cys Gly Ile Thr LysThr Tyr Thr Phe Arg Leu Asn 305 310 315 320 Glu His Pro Ser Ser His TrpSer Pro Gln Leu Ser Tyr Phe Glu Tyr 325 330 335 Arg Arg Leu Leu Arg AsnLeu Thr Ala Leu Leu Met Ile Arg Ala Thr 340 345 350 Tyr Gly Glu Tyr SerThr Gly Tyr Ile Asp Asn Val Thr Leu Val Ser 355 360 365 Ala Arg Pro ValLeu Gly Ala Pro Ala Pro Trp Val Glu Arg Cys Val 370 375 380 Cys Leu LeuGly Tyr Lys Gly Gln Phe Cys Gln Glu Cys Ala Ser Gly 385 390 395 400 TyrLys Arg Asp Ser Ala Arg Leu Gly Ala Phe Gly Ala Cys Val Pro 405 410 415Cys Asn Cys Gln Gly Glu Gly Ala Cys Asp Pro Asp Thr Gly Asp Cys 420 425430 Tyr Ser Gly Asp Glu Asn Pro Asp Ile Glu Cys Ala Asp Cys Pro Ile 435440 445 Gly Phe Tyr Asn Asp Pro His Asp Pro Arg Ser Cys Lys Pro Cys Pro450 455 460 Cys His Asn Gly Phe Ser Cys Ser Val Met Pro Glu Thr Glu GluVal 465 470 475 480 Val Cys Asn Asn Cys Pro Pro Gly Val Thr Gly Ala ArgCys Glu Leu 485 490 495 Cys Ala Asp Gly Phe Phe Gly Asp Pro Phe Gly GluHis Gly Pro Val 500 505 510 Arg Pro Cys Gln Arg Cys Gln Cys Asn Asn AsnVal Asp Pro Asn Ala 515 520 525 Ser Gly Asn Cys Asp Gln Leu Thr Gly ArgCys Leu Lys Cys Ile Tyr 530 535 540 Asn Thr Ala Gly Val Tyr Cys Asp GlnCys Lys Ala Gly Tyr Phe Gly 545 550 555 560 Asp Pro Leu Ala Pro Asn ProAla Asp Lys Cys Arg Ala Cys Asn Cys 565 570 575 Ser Pro Met Gly Ala GluPro Gly Glu Cys Arg Gly Asp Gly Ser Cys 580 585 590 Val Cys Lys Pro GlyPhe Gly Ala Phe Asn Cys Asp His Ala Ala Leu 595 600 605 Thr Ser Cys ProAla Cys Tyr Asn Gln Val Lys Ile Gln Met Asp Gln 610 615 620 Phe Thr GlnGln Leu Gln Ser Leu Glu Ala Leu Val Ser Lys Ala Gln 625 630 635 640 GlyGly Gly Gly Gly Gly Thr Val Pro Val Gln Leu Glu Gly Arg Ile 645 650 655Glu Gln Ala Glu Gln Ala Leu Gln Asp Ile Leu Gly Glu Ala Gln Ile 660 665670 Ser Glu Gly Ala Met Arg Ala Val Ala Val Arg Leu Ala Lys Ala Arg 675680 685 Ser Gln Glu Asn Asp Tyr Lys Thr Arg Leu Asp Asp Leu Lys Met Thr690 695 700 Ala Glu Arg Ile Arg Ala Leu Gly Ser Gln His Gln Asn Arg ValGln 705 710 715 720 Asp Thr Ser Arg Leu Ile Ser Gln Met Arg Leu Ser LeuAla Gly Ser 725 730 735 Glu Ala Leu Leu Glu Asn Thr Asn Ile His Ser SerGlu His Tyr Val 740 745 750 Gly Pro Asn Asp Phe Lys Ser Leu Ala Gln GluAla Thr Arg Lys Ala 755 760 765 Asp Ser His Ala Glu Ser Ala Asn Ala MetLys Gln Leu Ala Arg Glu 770 775 780 Thr Glu Asp Tyr Ser Lys Gln Ala LeuSer Leu Ala Arg Lys Leu Leu 785 790 795 800 Ser Gly Gly Gly Gly Ser GlySer Trp Asp Ser Ser Val Val Gln Gly 805 810 815 Leu Met Gly Lys Leu GluLys Thr Lys Ser Leu Ser Gln Gln Leu Ser 820 825 830 Leu Glu Gly Thr GlnAla Asp Ile Glu Ala Asp Arg Ser Tyr Gln His 835 840 845 Ser Leu Arg LeuLeu Asp Ser Ala Ser Gln Leu Gln Gly Val Ser Asp 850 855 860 Leu Ser PheGln Val Glu Ala Lys Arg Ile Arg Gln Lys Ala Asp Ser 865 870 875 880 LeuSer Asn Leu Val Thr Arg Gln Thr Asp Ala Phe Thr Arg Val Arg 885 890 895Asn Asn Leu Gly Asn Trp Glu Lys Glu Thr Arg Gln Leu Leu Gln Thr 900 905910 Gly Lys Asp Arg Arg Gln Thr Ser Asp Gln Leu Leu Ser Arg Ala Asn 915920 925 Leu Ala Lys Asn Arg Ala Gln Glu Ala Leu Ser Met Gly Asn Ala Thr930 935 940 Phe Tyr Glu Val Glu Asn Ile Leu Lys Asn Leu Arg Glu Phe AspLeu 945 950 955 960 Gln Val Glu Asp Arg Lys Ala Glu Ala Glu Glu Ala MetLys Arg Leu 965 970 975 Ser Ser Ile Ser Gln Lys Val Ala Asp Ala Ser AspLys Thr Gln Gln 980 985 990 Ala Glu Thr Ala Leu Gly Ser Ala Thr Ala AspThr Gln Arg Ala Lys 995 1000 1005 Asn Ala Ala Arg Glu Ala Leu Glu IleSer Ser Glu Ile Glu Leu Glu 1010 1015 1020 Ile Gly Ser Leu Asn Leu GluAla Asn Val Thr Ala Asp Gly Ala Leu 1025 1030 1035 1040 Ala Met Glu LysGly Thr Ala Thr Leu Lys Ser Glu Met Arg Glu Met 1045 1050 1055 Ile GluLeu Ala Arg Lys Glu Leu Glu Phe Asp Thr Asp Lys Asp Thr 1060 1065 1070Val Gln Leu Val Ile Thr Glu Ala Gln Gln Ala Asp Ala Arg Ala Thr 10751080 1085 Ser Ala Gly Val Thr Ile Gln Asp Thr Leu Asn Thr Leu Asp GlyIle 1090 1095 1100 Leu His Leu Ile Asp Gln Pro Gly Ser Val Asp Glu GluGly Met Met 1105 1110 1115 1120 Leu Leu Glu Gln Gly Leu Phe Gln Ala LysThr Gln Ile Asn Ser Arg 1125 1130 1135 Leu Arg Pro Leu Met Ser Asp LeuGlu Glu Arg Val Arg Arg Gln Arg 1140 1145 1150 Asn His Leu His Leu LeuGlu Thr Ser Ile Asp Gly Ile Leu Ala Asp 1155 1160 1165 Val Lys Asn LeuGlu Asn Ile Arg Asp Asn Leu Pro Pro Gly Cys Tyr 1170 1175 1180 Asn ThrGln Ala Leu Glu Gln Gln 118 1190 35 5057 DNA Mus musculus CDS(1)..(3513) unsure (3228) “r” can be a or g 35 acc tcc agg agg gaa gtctgt gat tgc aat ggg aag tcc agg caa tgt 48 Thr Ser Arg Arg Glu Val CysAsp Cys Asn Gly Lys Ser Arg Gln Cys 1 5 10 15 gtc ttt gat cag gag ctccat cga caa gca ggc agc ggg ttc cgt tgc 96 Val Phe Asp Gln Glu Leu HisArg Gln Ala Gly Ser Gly Phe Arg Cys 20 25 30 ctc aac tgc aat gac aat acagcg ggg gtt cac tgc gag cgg tcg agg 144 Leu Asn Cys Asn Asp Asn Thr AlaGly Val His Cys Glu Arg Ser Arg 35 40 45 gag ggg ttt tac cag cat cag agcaag agc cgc tgc cta ccc tgc aac 192 Glu Gly Phe Tyr Gln His Gln Ser LysSer Arg Cys Leu Pro Cys Asn 50 55 60 tgc cac tca aag ggt tcc ctc agt gctgga tgt gac aac tct gga caa 240 Cys His Ser Lys Gly Ser Leu Ser Ala GlyCys Asp Asn Ser Gly Gln 65 70 75 80 tgc agg tgt aag cca ggt gtg aca ggacaa aga tgt gac cag tgt cag 288 Cys Arg Cys Lys Pro Gly Val Thr Gly GlnArg Cys Asp Gln Cys Gln 85 90 95 cca ggc ttc cat atg ctc acc gat gct ggatgc acc cga gac cag ggg 336 Pro Gly Phe His Met Leu Thr Asp Ala Gly CysThr Arg Asp Gln Gly 100 105 110 caa cta gat tcc aag tgt gac tgt gac ccagct ggc atc tct gga ccc 384 Gln Leu Asp Ser Lys Cys Asp Cys Asp Pro AlaGly Ile Ser Gly Pro 115 120 125 tgt gat tct ggc cga tgt gtc tgc aaa ccagcc gtc act gga gag cgc 432 Cys Asp Ser Gly Arg Cys Val Cys Lys Pro AlaVal Thr Gly Glu Arg 130 135 140 tgt gat agg tgc cga cca cgt gac tat catctg gac cgg gca aac cct 480 Cys Asp Arg Cys Arg Pro Arg Asp Tyr His LeuAsp Arg Ala Asn Pro 145 150 155 160 gag ggc tgt acc cag tgt ttc tgc tatggg cat tca gcc agc tgc cac 528 Glu Gly Cys Thr Gln Cys Phe Cys Tyr GlyHis Ser Ala Ser Cys His 165 170 175 gcc tct gcc gac ttc agt gtc cac aaaatc act tca act ttc agt cag 576 Ala Ser Ala Asp Phe Ser Val His Lys IleThr Ser Thr Phe Ser Gln 180 185 190 gat gtg gat ggt tgg aag gcg gtt cagaga aac ggg gca cct gca aaa 624 Asp Val Asp Gly Trp Lys Ala Val Gln ArgAsn Gly Ala Pro Ala Lys 195 200 205 ctc cac tgg tca cag cgc cat cgg gacgtg ttt agt tct gcc cga aga 672 Leu His Trp Ser Gln Arg His Arg Asp ValPhe Ser Ser Ala Arg Arg 210 215 220 tca gac ccc gtc tat ttc gtg gcc cctgcc aaa ttc ctc ggt aac cag 720 Ser Asp Pro Val Tyr Phe Val Ala Pro AlaLys Phe Leu Gly Asn Gln 225 230 235 240 caa gtg agt tac ggg cag agc ctgtct ttt gac tac cgc gtg gac aga 768 Gln Val Ser Tyr Gly Gln Ser Leu SerPhe Asp Tyr Arg Val Asp Arg 245 250 255 gga ggt aga cag ccg tct gcc tacgat gtg atc ctg gaa ggt gct ggt 816 Gly Gly Arg Gln Pro Ser Ala Tyr AspVal Ile Leu Glu Gly Ala Gly 260 265 270 cta cag atc aga gct cct ctg atggct cca ggc aag aca ctt cct tgt 864 Leu Gln Ile Arg Ala Pro Leu Met AlaPro Gly Lys Thr Leu Pro Cys 275 280 285 ggg atc aca aag act tac aca ttcaga ctg aat gaa cat cca agc agt 912 Gly Ile Thr Lys Thr Tyr Thr Phe ArgLeu Asn Glu His Pro Ser Ser 290 295 300 cac tgg agt ccc cag ctg agt tatttc gaa tat cga agg tta ctg cgg 960 His Trp Ser Pro Gln Leu Ser Tyr PheGlu Tyr Arg Arg Leu Leu Arg 305 310 315 320 aac ctc aca gcc ctc ctg atgatc cga gct acg tac gga gaa tat agt 1008 Asn Leu Thr Ala Leu Leu Met IleArg Ala Thr Tyr Gly Glu Tyr Ser 325 330 335 aca ggg tac att gat aac gtgacc ctg gtt tca gcc cgc cct gtc ctt 1056 Thr Gly Tyr Ile Asp Asn Val ThrLeu Val Ser Ala Arg Pro Val Leu 340 345 350 gga gcc cca gcc cct tgg gttgaa cgt tgt gta tgc ctg ctg ggg tac 1104 Gly Ala Pro Ala Pro Trp Val GluArg Cys Val Cys Leu Leu Gly Tyr 355 360 365 aag gga caa ttc tgc cag gaatgt gct tct ggt tac aaa aga gat tcg 1152 Lys Gly Gln Phe Cys Gln Glu CysAla Ser Gly Tyr Lys Arg Asp Ser 370 375 380 gca aga ttg ggc gct ttt ggcgcc tgt gtt ccc tgt aac tgc caa ggg 1200 Ala Arg Leu Gly Ala Phe Gly AlaCys Val Pro Cys Asn Cys Gln Gly 385 390 395 400 gag ggg gcc tgt gat ccagac acg gga gat tgc tac tcg ggg gac gag 1248 Glu Gly Ala Cys Asp Pro AspThr Gly Asp Cys Tyr Ser Gly Asp Glu 405 410 415 aat cct gac att gag tgtgct gac tgt ccc atc ggt ttc tac aat gac 1296 Asn Pro Asp Ile Glu Cys AlaAsp Cys Pro Ile Gly Phe Tyr Asn Asp 420 425 430 cca cat gac ccc cgc agctgc aag cca tgt ccc tgt cac aat ggg ttc 1344 Pro His Asp Pro Arg Ser CysLys Pro Cys Pro Cys His Asn Gly Phe 435 440 445 agc tgt tca gtg atg cctgag aca gag gag gtg gtg tgt aac aac tgt 1392 Ser Cys Ser Val Met Pro GluThr Glu Glu Val Val Cys Asn Asn Cys 450 455 460 ccc cct ggg gtc aca ggtgcc cgc tgt gag ctc tgt gct gat ggc ttc 1440 Pro Pro Gly Val Thr Gly AlaArg Cys Glu Leu Cys Ala Asp Gly Phe 465 470 475 480 ttt ggg gat ccc tttggg gaa cat ggc cca gtg agg cct tgt caa cgc 1488 Phe Gly Asp Pro Phe GlyGlu His Gly Pro Val Arg Pro Cys Gln Arg 485 490 495 tgc caa tgc aac aacaac gtg gac ccc aat gcc tct ggg aac tgt gac 1536 Cys Gln Cys Asn Asn AsnVal Asp Pro Asn Ala Ser Gly Asn Cys Asp 500 505 510 cag ttg aca ggc agatgc ttg aaa tgt atc tac aac acg gcc ggt gtc 1584 Gln Leu Thr Gly Arg CysLeu Lys Cys Ile Tyr Asn Thr Ala Gly Val 515 520 525 tac tgt gac cag tgcaaa gca ggt tac ttt gga gac cca ttg gct ccc 1632 Tyr Cys Asp Gln Cys LysAla Gly Tyr Phe Gly Asp Pro Leu Ala Pro 530 535 540 aac cca gca gac aagtgt cga gct tgc aac tgc agc ccc atg ggt gcg 1680 Asn Pro Ala Asp Lys CysArg Ala Cys Asn Cys Ser Pro Met Gly Ala 545 550 555 560 gag cct gga gagtgt cga ggt gat ggc agc tgt gtt tgc aag cca ggc 1728 Glu Pro Gly Glu CysArg Gly Asp Gly Ser Cys Val Cys Lys Pro Gly 565 570 575 ttt ggc gcc ttcaac tgt gat cac gca gcc cta acc agt tgt cct gct 1776 Phe Gly Ala Phe AsnCys Asp His Ala Ala Leu Thr Ser Cys Pro Ala 580 585 590 tgc tac aat caagtg aag att cag atg gac cag ttt acc cag cag ctc 1824 Cys Tyr Asn Gln ValLys Ile Gln Met Asp Gln Phe Thr Gln Gln Leu 595 600 605 cag agc ctg gaggcc ctg gtt tca aag gct cag ggt ggt ggt ggt ggt 1872 Gln Ser Leu Glu AlaLeu Val Ser Lys Ala Gln Gly Gly Gly Gly Gly 610 615 620 ggt aca gtc ccagtg cag ctg gaa ggc agg atc gag cag gct gag cag 1920 Gly Thr Val Pro ValGln Leu Glu Gly Arg Ile Glu Gln Ala Glu Gln 625 630 635 640 gcc ctt caggac att ctg gga gaa gct cag att tca gaa ggg gca atg 1968 Ala Leu Gln AspIle Leu Gly Glu Ala Gln Ile Ser Glu Gly Ala Met 645 650 655 aga gcc gttgct gtc cgg ctg gcc aag gca agg agc caa gag aac gac 2016 Arg Ala Val AlaVal Arg Leu Ala Lys Ala Arg Ser Gln Glu Asn Asp 660 665 670 tac aag acccgc ctg gat gac ctc aag atg act gca gaa agg atc cgg 2064 Tyr Lys Thr ArgLeu Asp Asp Leu Lys Met Thr Ala Glu Arg Ile Arg 675 680 685 gcc ctg ggcagt cag cat cag aac aga gtt cag gat acg agc aga ctc 2112 Ala Leu Gly SerGln His Gln Asn Arg Val Gln Asp Thr Ser Arg Leu 690 695 700 atc tct cagatg cgc ctg agt ctg gca gga agc gaa gct ctc ttg gaa 2160 Ile Ser Gln MetArg Leu Ser Leu Ala Gly Ser Glu Ala Leu Leu Glu 705 710 715 720 aac actaat atc cat tct tct gag cac tac gtg ggg ccg aat gat ttt 2208 Asn Thr AsnIle His Ser Ser Glu His Tyr Val Gly Pro Asn Asp Phe 725 730 735 aaa agtctg gct cag gag gct aca aga aag gca gac agc cac gct gag 2256 Lys Ser LeuAla Gln Glu Ala Thr Arg Lys Ala Asp Ser His Ala Glu 740 745 750 tca gctaac gca atg aag caa cta gca agg gaa act gag gac tac tcc 2304 Ser Ala AsnAla Met Lys Gln Leu Ala Arg Glu Thr Glu Asp Tyr Ser 755 760 765 aaa caagca ctt tca ttg gcc cgc aag ctc ttg agt gga gga ggc gga 2352 Lys Gln AlaLeu Ser Leu Ala Arg Lys Leu Leu Ser Gly Gly Gly Gly 770 775 780 agt ggctct tgg gac agc tcc gtg gta caa ggt ctt atg gga aaa tta 2400 Ser Gly SerTrp Asp Ser Ser Val Val Gln Gly Leu Met Gly Lys Leu 785 790 795 800 gagaaa acc aag tcc ctg agc cag cag ctg tca ttg gag ggc acc caa 2448 Glu LysThr Lys Ser Leu Ser Gln Gln Leu Ser Leu Glu Gly Thr Gln 805 810 815 gccgac att gaa gct gat agg tcg tat cag cac agt ctc cgc ctc ctg 2496 Ala AspIle Glu Ala Asp Arg Ser Tyr Gln His Ser Leu Arg Leu Leu 820 825 830 gattct gcc tct cag ctt cag gga gtc agt gat ctg tcc ttt cag gtg 2544 Asp SerAla Ser Gln Leu Gln Gly Val Ser Asp Leu Ser Phe Gln Val 835 840 845 gaagca aag agg atc aga caa aag gct gat tct ctc tca aac ctg gtg 2592 Glu AlaLys Arg Ile Arg Gln Lys Ala Asp Ser Leu Ser Asn Leu Val 850 855 860 accaga caa acg gat gca ttc acg cgt gtg cga aac aat ctg ggg aac 2640 Thr ArgGln Thr Asp Ala Phe Thr Arg Val Arg Asn Asn Leu Gly Asn 865 870 875 880tgg gaa aaa gaa aca cgg cag ctt tta cag act gga aag gat agg aga 2688 TrpGlu Lys Glu Thr Arg Gln Leu Leu Gln Thr Gly Lys Asp Arg Arg 885 890 895cag act tca gat cag ctg ctt tcc cgt gcc aac ctt gct aaa aac aga 2736 GlnThr Ser Asp Gln Leu Leu Ser Arg Ala Asn Leu Ala Lys Asn Arg 900 905 910gcc caa gaa gcg cta agt atg ggc aat gcc act ttt tat gaa gtt gag 2784 AlaGln Glu Ala Leu Ser Met Gly Asn Ala Thr Phe Tyr Glu Val Glu 915 920 925aac atc ctg aag aac ctc cga gag ttt gat ctg cag gtt gaa gac aga 2832 AsnIle Leu Lys Asn Leu Arg Glu Phe Asp Leu Gln Val Glu Asp Arg 930 935 940aaa gca gag gct gaa gag gcc atg aag aga ctc tcc tct att agc cag 2880 LysAla Glu Ala Glu Glu Ala Met Lys Arg Leu Ser Ser Ile Ser Gln 945 950 955960 aag gtt gcg gat gcc agt gac aag acc cag caa gca gaa acg gcc ctg 2928Lys Val Ala Asp Ala Ser Asp Lys Thr Gln Gln Ala Glu Thr Ala Leu 965 970975 ggg agc gcc act gcc gac acc caa cgg gca aag aac gca gct agg gag 2976Gly Ser Ala Thr Ala Asp Thr Gln Arg Ala Lys Asn Ala Ala Arg Glu 980 985990 gcc ctg gag atc agc agc gag ata gag ctg gag ata ggg agt ctg aac 3024Ala Leu Glu Ile Ser Ser Glu Ile Glu Leu Glu Ile Gly Ser Leu Asn 995 10001005 ttg gaa gct aat gtg aca gca gat ggg gcc ttg gcc atg gag aaa ggg3072 Leu Glu Ala Asn Val Thr Ala Asp Gly Ala Leu Ala Met Glu Lys Gly1010 1015 1020 act gcc act ctg aag agc gag atg aga gag atg att gag ctggcc aga 3120 Thr Ala Thr Leu Lys Ser Glu Met Arg Glu Met Ile Glu Leu AlaArg 1025 1030 1035 1040 aag gag ctg gag ttt gac acg gat aag gac acg gtgcag ctg gtg att 3168 Lys Glu Leu Glu Phe Asp Thr Asp Lys Asp Thr Val GlnLeu Val Ile 1045 1050 1055 act gaa gcc cag caa gct gat gcc aga gcc acgagt gcc gga gtt acc 3216 Thr Glu Ala Gln Gln Ala Asp Ala Arg Ala Thr SerAla Gly Val Thr 1060 1065 1070 atc caa gac acr ctc aac aca ttg gac ggcatc cta cac ctc ata gac 3264 Ile Gln Asp Thr Leu Asn Thr Leu Asp Gly IleLeu His Leu Ile Asp 1075 1080 1085 cag cct ggc agt gtg gat gaa gaa gggatg atg cta tta gaa caa ggg 3312 Gln Pro Gly Ser Val Asp Glu Glu Gly MetMet Leu Leu Glu Gln Gly 1090 1095 1100 ctt ttc caa gcc aag acc cag atcaac agt cga ctt cgg ccc ttg atg 3360 Leu Phe Gln Ala Lys Thr Gln Ile AsnSer Arg Leu Arg Pro Leu Met 1105 1110 1115 1120 tct gac ctg gag gag agggtg cgt cgg cag agg aac cac ctc cat ctg 3408 Ser Asp Leu Glu Glu Arg ValArg Arg Gln Arg Asn His Leu His Leu 1125 1130 1135 ctg gag act agc atagat gga att ctt gct gat gtg aag aac ctg gag 3456 Leu Glu Thr Ser Ile AspGly Ile Leu Ala Asp Val Lys Asn Leu Glu 1140 1145 1150 aac att cga gacaac ctg ccc cca ggc tgc tac aat acc caa gct ctt 3504 Asn Ile Arg Asp AsnLeu Pro Pro Gly Cys Tyr Asn Thr Gln Ala Leu 1155 1160 1165 gag caa cagtgaagttgtc atagagattt gtccactgtt gtgaaaggac 3553 Glu Gln Gln 1170acagacctca ggggtcagga gccatctcgt gtggatgggc tgtgctcagg ctatctgaac 3613acatttaatg ggtttgttca ggtccaattc catccctgag accatgggct gtggatgtct 3673tcctgtacca atataatact gtttgtactt cctgatgctg gcagtgaggc agatagcatt 3733gagtatgaga ttgatcaagg agggacaaat cgtgcgctca gaacagtgac aaactgaatt 3793ctgggcagtg aggcagatag cattgagtat gagattgatc aaggacctgg accccaaaga 3853tagactggat ggaaagacaa actgcacagg cagatgtttg cctcataata gtcgtaagtg 3913gagtcctgga atttggtcag aacagtgaaa aactggaatt ctgggatata gaaagatcct 3973gctgctatgt caggacaaag tgagatctaa tcccgctgcg gccagcaaag tactcttgct 4033tcacccacta gacgtttttt gtccaccaca tttcctccag tgcccaccca atacatgagt 4093atgtcctcca cttcatgctg agtgcagaga gcagtgatgg tatagatctg gaaatctggc 4153ccatgtggag cagtggtgcc cgcctgcacc cctaaccttc atgctctcgg cctgagtgtg 4213acagcctttc tcctaatggt gcgaacaact tagaggctgt atttttttat gaaagcatct 4273tttaccagcc aagcaatcat tgggaaagta tttctttgag tttcaaagtg atataagaaa 4333tgtgtctggc actaaaggaa gtggagttat ctaaaagata tattcatcat aatccaatct 4393tcctttggaa acactaaaac tcatatacat ctgtgtattg tatcttattt tctctttctc 4453ctctctcttt cctccaccca taataagaga atgttcctac tcacacttca gctgggtcac 4513atccatccct ccattcatcc ttccatccat ctttccatcc attacctcca tccagccttc 4573taacatatat ttattgcgtc actactgtgt gccaggggtg agtggaacag tatggacagt 4633ctctactctc atggagttga gtgtctagtg agagaacaac attagaataa gtaaatggaa 4693actcccatgc cttgttcatc tcatgtgata tttattgcag tcacccaccc tttggtttga 4753aacctctttt cttaataatg tgttgcaaga cattcccatg agggtacttg agttagagca 4813aagttgagat cgctctgagt tgtacacatt tctctatgtt ccagccgtct ctccacccct 4873tccacacaga ctgtgcacag actggtgcat cagggcaata ccagtgggaa ttgctgaagg 4933aaccagaggc attgggacct cagtttggaa gactactgta ctgtctcacc tctgtacttc 4993cttgtctttt catggatgtg ttattaaata aagaacgagt gttagatgct aaaaaaaaaa 5053aaaa 5057 36 1171 PRT Mus musculus 36 Thr Ser Arg Arg Glu Val Cys AspCys Asn Gly Lys Ser Arg Gln Cys 1 5 10 15 Val Phe Asp Gln Glu Leu HisArg Gln Ala Gly Ser Gly Phe Arg Cys 20 25 30 Leu Asn Cys Asn Asp Asn ThrAla Gly Val His Cys Glu Arg Ser Arg 35 40 45 Glu Gly Phe Tyr Gln His GlnSer Lys Ser Arg Cys Leu Pro Cys Asn 50 55 60 Cys His Ser Lys Gly Ser LeuSer Ala Gly Cys Asp Asn Ser Gly Gln 65 70 75 80 Cys Arg Cys Lys Pro GlyVal Thr Gly Gln Arg Cys Asp Gln Cys Gln 85 90 95 Pro Gly Phe His Met LeuThr Asp Ala Gly Cys Thr Arg Asp Gln Gly 100 105 110 Gln Leu Asp Ser LysCys Asp Cys Asp Pro Ala Gly Ile Ser Gly Pro 115 120 125 Cys Asp Ser GlyArg Cys Val Cys Lys Pro Ala Val Thr Gly Glu Arg 130 135 140 Cys Asp ArgCys Arg Pro Arg Asp Tyr His Leu Asp Arg Ala Asn Pro 145 150 155 160 GluGly Cys Thr Gln Cys Phe Cys Tyr Gly His Ser Ala Ser Cys His 165 170 175Ala Ser Ala Asp Phe Ser Val His Lys Ile Thr Ser Thr Phe Ser Gln 180 185190 Asp Val Asp Gly Trp Lys Ala Val Gln Arg Asn Gly Ala Pro Ala Lys 195200 205 Leu His Trp Ser Gln Arg His Arg Asp Val Phe Ser Ser Ala Arg Arg210 215 220 Ser Asp Pro Val Tyr Phe Val Ala Pro Ala Lys Phe Leu Gly AsnGln 225 230 235 240 Gln Val Ser Tyr Gly Gln Ser Leu Ser Phe Asp Tyr ArgVal Asp Arg 245 250 255 Gly Gly Arg Gln Pro Ser Ala Tyr Asp Val Ile LeuGlu Gly Ala Gly 260 265 270 Leu Gln Ile Arg Ala Pro Leu Met Ala Pro GlyLys Thr Leu Pro Cys 275 280 285 Gly Ile Thr Lys Thr Tyr Thr Phe Arg LeuAsn Glu His Pro Ser Ser 290 295 300 His Trp Ser Pro Gln Leu Ser Tyr PheGlu Tyr Arg Arg Leu Leu Arg 305 310 315 320 Asn Leu Thr Ala Leu Leu MetIle Arg Ala Thr Tyr Gly Glu Tyr Ser 325 330 335 Thr Gly Tyr Ile Asp AsnVal Thr Leu Val Ser Ala Arg Pro Val Leu 340 345 350 Gly Ala Pro Ala ProTrp Val Glu Arg Cys Val Cys Leu Leu Gly Tyr 355 360 365 Lys Gly Gln PheCys Gln Glu Cys Ala Ser Gly Tyr Lys Arg Asp Ser 370 375 380 Ala Arg LeuGly Ala Phe Gly Ala Cys Val Pro Cys Asn Cys Gln Gly 385 390 395 400 GluGly Ala Cys Asp Pro Asp Thr Gly Asp Cys Tyr Ser Gly Asp Glu 405 410 415Asn Pro Asp Ile Glu Cys Ala Asp Cys Pro Ile Gly Phe Tyr Asn Asp 420 425430 Pro His Asp Pro Arg Ser Cys Lys Pro Cys Pro Cys His Asn Gly Phe 435440 445 Ser Cys Ser Val Met Pro Glu Thr Glu Glu Val Val Cys Asn Asn Cys450 455 460 Pro Pro Gly Val Thr Gly Ala Arg Cys Glu Leu Cys Ala Asp GlyPhe 465 470 475 480 Phe Gly Asp Pro Phe Gly Glu His Gly Pro Val Arg ProCys Gln Arg 485 490 495 Cys Gln Cys Asn Asn Asn Val Asp Pro Asn Ala SerGly Asn Cys Asp 500 505 510 Gln Leu Thr Gly Arg Cys Leu Lys Cys Ile TyrAsn Thr Ala Gly Val 515 520 525 Tyr Cys Asp Gln Cys Lys Ala Gly Tyr PheGly Asp Pro Leu Ala Pro 530 535 540 Asn Pro Ala Asp Lys Cys Arg Ala CysAsn Cys Ser Pro Met Gly Ala 545 550 555 560 Glu Pro Gly Glu Cys Arg GlyAsp Gly Ser Cys Val Cys Lys Pro Gly 565 570 575 Phe Gly Ala Phe Asn CysAsp His Ala Ala Leu Thr Ser Cys Pro Ala 580 585 590 Cys Tyr Asn Gln ValLys Ile Gln Met Asp Gln Phe Thr Gln Gln Leu 595 600 605 Gln Ser Leu GluAla Leu Val Ser Lys Ala Gln Gly Gly Gly Gly Gly 610 615 620 Gly Thr ValPro Val Gln Leu Glu Gly Arg Ile Glu Gln Ala Glu Gln 625 630 635 640 AlaLeu Gln Asp Ile Leu Gly Glu Ala Gln Ile Ser Glu Gly Ala Met 645 650 655Arg Ala Val Ala Val Arg Leu Ala Lys Ala Arg Ser Gln Glu Asn Asp 660 665670 Tyr Lys Thr Arg Leu Asp Asp Leu Lys Met Thr Ala Glu Arg Ile Arg 675680 685 Ala Leu Gly Ser Gln His Gln Asn Arg Val Gln Asp Thr Ser Arg Leu690 695 700 Ile Ser Gln Met Arg Leu Ser Leu Ala Gly Ser Glu Ala Leu LeuGlu 705 710 715 720 Asn Thr Asn Ile His Ser Ser Glu His Tyr Val Gly ProAsn Asp Phe 725 730 735 Lys Ser Leu Ala Gln Glu Ala Thr Arg Lys Ala AspSer His Ala Glu 740 745 750 Ser Ala Asn Ala Met Lys Gln Leu Ala Arg GluThr Glu Asp Tyr Ser 755 760 765 Lys Gln Ala Leu Ser Leu Ala Arg Lys LeuLeu Ser Gly Gly Gly Gly 770 775 780 Ser Gly Ser Trp Asp Ser Ser Val ValGln Gly Leu Met Gly Lys Leu 785 790 795 800 Glu Lys Thr Lys Ser Leu SerGln Gln Leu Ser Leu Glu Gly Thr Gln 805 810 815 Ala Asp Ile Glu Ala AspArg Ser Tyr Gln His Ser Leu Arg Leu Leu 820 825 830 Asp Ser Ala Ser GlnLeu Gln Gly Val Ser Asp Leu Ser Phe Gln Val 835 840 845 Glu Ala Lys ArgIle Arg Gln Lys Ala Asp Ser Leu Ser Asn Leu Val 850 855 860 Thr Arg GlnThr Asp Ala Phe Thr Arg Val Arg Asn Asn Leu Gly Asn 865 870 875 880 TrpGlu Lys Glu Thr Arg Gln Leu Leu Gln Thr Gly Lys Asp Arg Arg 885 890 895Gln Thr Ser Asp Gln Leu Leu Ser Arg Ala Asn Leu Ala Lys Asn Arg 900 905910 Ala Gln Glu Ala Leu Ser Met Gly Asn Ala Thr Phe Tyr Glu Val Glu 915920 925 Asn Ile Leu Lys Asn Leu Arg Glu Phe Asp Leu Gln Val Glu Asp Arg930 935 940 Lys Ala Glu Ala Glu Glu Ala Met Lys Arg Leu Ser Ser Ile SerGln 945 950 955 960 Lys Val Ala Asp Ala Ser Asp Lys Thr Gln Gln Ala GluThr Ala Leu 965 970 975 Gly Ser Ala Thr Ala Asp Thr Gln Arg Ala Lys AsnAla Ala Arg Glu 980 985 990 Ala Leu Glu Ile Ser Ser Glu Ile Glu Leu GluIle Gly Ser Leu Asn 995 1000 1005 Leu Glu Ala Asn Val Thr Ala Asp GlyAla Leu Ala Met Glu Lys Gly 1010 1015 1020 Thr Ala Thr Leu Lys Ser GluMet Arg Glu Met Ile Glu Leu Ala Arg 1025 1030 1035 1040 Lys Glu Leu GluPhe Asp Thr Asp Lys Asp Thr Val Gln Leu Val Ile 1045 1050 1055 Thr GluAla Gln Gln Ala Asp Ala Arg Ala Thr Ser Ala Gly Val Thr 1060 1065 1070Ile Gln Asp Thr Leu Asn Thr Leu Asp Gly Ile Leu His Leu Ile Asp 10751080 1085 Gln Pro Gly Ser Val Asp Glu Glu Gly Met Met Leu Leu Glu GlnGly 1090 1095 1100 Leu Phe Gln Ala Lys Thr Gln Ile Asn Ser Arg Leu ArgPro Leu Met 1105 1110 1115 1120 Ser Asp Leu Glu Glu Arg Val Arg Arg GlnArg Asn His Leu His Leu 1125 1130 1135 Leu Glu Thr Ser Ile Asp Gly IleLeu Ala Asp Val Lys Asn Leu Glu 1140 1145 1150 Asn Ile Arg Asp Asn LeuPro Pro Gly Cys Tyr Asn Thr Gln Ala Leu 1155 1160 1165 Glu Gln Gln 1170

We claim:
 1. Recombinant laminin 5-expressing cells.
 2. The recombinantlaminin 5-expressing cells of claim 1, wherein the cells expressrecombinant laminin 5 comprising: a first chain comprising a polypeptidethat is substantially similar to an α3 laminin chain; a second chaincomprising a polypeptide that is substantially similar to a β3 lamininchain; and a third chain comprising a polypeptide that is substantiallysimilar to a γ2 laminin chain; wherein the first, second, and thirdchains are assembled into recombinant heterotrimeric laminin
 5. 3. Therecombinant laminin 5-expressing cells of claim 1, wherein the cellsexpress recombinant laminin 5 comprising: a first chain comprising arecombinant polypeptide that is at least 70% identical to one or more ofSEQ ID NO:2, 4, 6, 8, 10, 12, or fragments thereof; a second chaincomprising a recombinant polypeptide that is at least 70% identical toone or more of SEQ ID NO:14, 16, 18, 20, 22, 24, or fragments thereof;and a third chain comprising a recombinant polypeptide that is at least70% identical to one or more of SEQ ID NO:26, 28, 30, 32, 34, 36, orfragments thereof; wherein the cell expresses the first, second, andthird chains, and wherein the first, second, and third chains assembleinto recombinant heterotrimeric laminin 5 that is secreted into themedia by the cultured cell.
 4. The recombinant laminin 5-expressingcells of claim 1, wherein the cells express recombinant laminin 5comprising: a first chain encoded by a polynucleotide that hybridizesunder high stringency conditions to a coding region of one or more ofSEQ ID NO:1, 3, 5, 7, 9, 11, or fragments thereof; a second chainencoded by a polynucleotide that hybridizes under high stringencyconditions to a coding region of one or more of SEQ ID NO: 13, 15, 17,19, 21, 23, or fragments thereof; and a third chain encoded by apolynucleotide that hybridizes under high stringency conditions to acoding region of one or more of SEQ ID NO: 25, 27, 29, 31, 33, 35, orfragments thereof; wherein the cell expresses the first, second, andthird chains, and wherein the first, second, and third chains assembleinto recombinant heterotrimeric laminin 5 that is secreted into themedia by the cultured cell.
 5. The recombinant laminin 5-expressing hostcells of claim 1, wherein the cells express recombinant laminin 5comprising a first, second, and third polypeptide chain, wherein thefirst, second, and third polypeptide chains each comprise a generalstructure selected from the group consisting of: (1) R1-R2-R3; (2)R1-R2-R3(e); (3) R3; (4) R3(e); (5) R1-R3; (6) R1-R3(e); (7) R2-R3; and(8) R2-R3(e) wherein R1 is a amino terminal methionine; R2 is a signalsequence that is capable of directing secretion of the polypeptide,wherein the signal sequence may be the natural signal sequence for theparticular laminin chain, that of another secreted protein, or it may bean artificial sequence; R3 is a secreted α3 laminin chain for the firstpolypeptide chain, a secreted β3 laminin chain for the secondpolypeptide chain, and γ2 laminin chain for the third polypeptide chain;and R3(e) is identical to R3, but further comprises an epitope tag.
 6. Amethod of purifying recombinant laminin 5, comprising: a. providing theeukaryotic cells of any one of claim 1-5; b. growing the cells in cellculture medium under conditions to stimulate expression of therecombinant laminin 5 chains; c. passing the cell culture medium throughan affinity chromatography column, wherein the column contains acompound that specifically binds to the epitope tag; d. washing theaffinity column to remove unbound materials; and e. eluting the boundrecombinant laminin 5 from the column.
 7. Purified recombinant laminin 5isolated according to the method of claim
 6. 8. Purified recombinantlaminin
 5. 9. The substantially purified recombinant laminin 5 of claim8 comprising: a first chain comprising a polypeptide that issubstantially similar to an α3 laminin chain; a second chain comprisinga polypeptide that is substantially similar to a β3 laminin chain; and athird chain comprising a polypeptide that is substantially similar to aγ2 laminin chain; wherein the first, second, and third chains areassembled into recombinant heterotrimeric laminin
 5. 10. The purifiedrecombinant laminin 5 of claim 8, comprising: a first chain comprising arecombinant polypeptide that is at least 70% identical to one or more ofSEQ ID NO:2, 4, 6, 8, 10, 12, or fragments thereof; a second chaincomprising a recombinant polypeptide that is at least 70% identical toone or more of SEQ ID NO:14, 16, 18, 20, 22, 24, or fragments thereof;and a third chain comprising a recombinant polypeptide that is at least70% identical to one or more of SEQ ID NO:26, 28, 30, 32, 34, 36, orfragments thereof; wherein the first, second, and third chains areassembled into recombinant heterotrimeric laminin
 5. 11. The purifiedrecombinant laminin 5 of claim 8, comprising: a first chain encoded by apolynucleotide that hybridizes under high stringency conditions to acoding region of one or more of SEQ ID NO:1, 3, 5, 7, 9, 11, orfragments thereof; a second chain encoded by a polynucleotide thathybridizes under high stringency conditions to a coding region of one ormore of SEQ ID NO:13, 15, 17, 19, 21, 23, or fragments thereof; and athird chain encoded by a polynucleotide that hybridizes under highstringency conditions to a coding region of SEQ ID NO:25, 27, 29, 31,33, 35, or fragments thereof; wherein the first, second, and thirdchains are assembled into recombinant heterotrimeric laminin
 5. 12. Thepurified recombinant heterotrimeric laminin 5 of claim 8, comprising afirst, second, and third polypeptide chain, wherein the first, second,and third polypeptide chains each comprise a general structure selectedfrom the group consisting of: (1) R1-R2-R3; (2) R1-R2-R3(e); (3) R3; (4)R3(e); (5) R1-R3; (6) R1-R3(e); (7) R2-R3; and (8) R2-R3(e) wherein R1is a amino terminal methionine; R2 is a signal sequence that is capableof directing secretion of the polypeptide, wherein the signal sequencemay be the natural signal sequence for the particular laminin chain,that of another secreted protein, or it may be an artificial sequence;R3 is a secreted α3 laminin chain for the first polypeptide chain, asecreted β3 laminin chain for the second polypeptide chain, and asecreted γ2 laminin chain for the third polypeptide chain; and R3(e) isidentical to R3, but further comprises an epitope tag.
 13. Apharmaceutical composition comprising: a. the recombinant laminin 5 ofany of claims 7-12; and b. a pharmaceutically acceptable carrier.
 14. Amethod for accelerating wound healing comprising administering to apatient in need thereof an amount effective of the recombinant laminin 5of any of claims 7-12 to accelerate wound healing.
 15. The method ofclaim 14 wherein the wound is selected from the group consisting ofdiabetic foot ulcers, venous ulcers, pressure sores, skin surgery,burns, acute wounds, skin grafts, corneal ulcerations, gastro-intestinalulcers, periodontitis, and gingivitis.
 16. A method to improve thebiocompatibility of a medical device, comprising contacting the medicaldevice with an amount effective of the recombinant laminin 5 of any ofclaims 7-12 to improve the biocompatibility of the medical device.
 17. Amethod to promote cell adhesion to a surface, comprising contacting thecells with an amount effective of the recombinant laminin 5 of any ofclaims 7-12 to promote cell adhesion to a surface.
 18. An improvedmethod for the ex vivo treatment of Type I diabetes in a patient in needthereof, wherein the improvement consists of culturing isolatedpancreatic islet beta in the presence of an amount effective therecombinant laminin 5 of any of claims 7-12 to promote adhesion of thepancreatic islet beta cells to a surface, culturing the cells, andre-introducing the cells into the patient.
 19. A method for regulatingangiogenesis, comprising contacting a tissue in need thereof with anamount effective to promote angiogenesis of laminin 5 to regulateangiogenesis.
 20. The method of claim 19, wherein the laminin 5comprises recombinant laminin 5 according to any one of claims 7-12. 21.An improved cell growth substrate, wherein the improvement consists ofproviding a cell growth substrate that has been coated with an amounteffective of the recombinant laminin 5 of any of claims 7-12 to promotecell attachment to the cell growth substrate.
 22. An improved cellculture medium, wherein the improvement consists of providing an amounteffective of the recombinant laminin 5 of any of claims 7-12 to promotecell attachment to a cell growth substrate.
 23. An improved medicalimplantation device, wherein the improvement consists of providing amedical implantation device that has been coated with an amounteffective of the recombinant laminin 5 of any of claims 7-12 to promotecell attachment to the medical implantation device.
 24. The improvedmedical implantation device of claim 23, wherein the medicalimplantation device is selected from the group consisting of artificialgrafts, indwelling or transcutaneous catheter, polytetrafluoroethylene,expanded polytetrafluoroethylene, needle, metal pin, metal rod,colostomy tube, transcutaneous catheter, dental abutment piece orsurgical mesh.
 25. A method for accelerating wound healing comprisingadministering to a patient in need thereof an amount effective of thepharmaceutical composition of claim 13 to accelerate wound healing. 26.The method of claim 25 wherein the wound is selected from the groupconsisting of diabetic foot ulcers, venous ulcers, pressure sores, skinsurgery, burns, acute wounds, skin grafts, corneal ulcerations,gastrointestinal ulcers, periodontitis, and gingivitis.
 27. A method toimprove the biocompatibility of a medical device, comprising contactingthe medical device with an amount effective of the pharmaceuticalcomposition of claim 13 to improve the biocompatibility of the medicaldevice.
 28. A method to promote cell adhesion to a surface, comprisingcontacting the cells with an amount effective of the pharmaceuticalcomposition of claim 13 to promote cell adhesion to a surface.
 29. Animproved method for the ex vivo treatment of Type I diabetes in apatient in need thereof, wherein the improvement consists of culturingisolated pancreatic islet beta in the presence of an amount effectivethe pharmaceutical composition of claim 13 to promote adhesion of thepancreatic islet beta cells to a surface, culturing the cells, andre-introducing the cells into the patient.
 30. A method for regulatingangiogenesis, comprising contacting a tissue in need thereof with anamount effective to regulate angiogenesis of the pharmaceuticalcomposition of claim 13 to regulate angiogenesis.
 31. An improved cellgrowth substrate, wherein the improvement consists of providing a cellgrowth substrate that has been coated with an amount effective of thepharmaceutical composition of claim 13 to promote cell attachment to thecell growth substrate.
 32. An improved medical implantation device,wherein the improvement consists of providing a medical implantationdevice that has been coated with an amount effective of thepharmaceutical composition of claim 13 to promote cell attachment to themedical implantation device.
 33. The improved medical implantationdevice of claim 32, wherein the medical implantation device is selectedfrom the group consisting of artificial grafts, indwelling ortranscutaneous catheter, polytetrafluoroethylene, expandedpolytetrafluoroethylene, needle, metal pin, metal rod, colostomy tube,transcutaneous catheter, dental abutment piece or surgical mesh.
 34. Anisolated polynucleotide sequence selected from the group consisting ofSEQ ID 21, SEQ ID NO:23, SEQ ID NO:29, SEQ ID NO:31.
 35. An isolatedpolypeptide sequence selected from the group consisting of SEQ ID NO:22,SEQ ID NO:24, SEQ ID NO:30, and SEQ ID NO:32.